Current Management of T1 Colon Cancer in Denmark: A Nationwide Cohort Study.

OBJECTIVE: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry. BACKGROUND: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge. METHODS: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival. RESULTS: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis. CONCLUSIONS: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed.

The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND: There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins. METHODS: Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival. RESULTS: A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion. CONCLUSIONS: In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.

Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study.

AIM: Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. METHOD: This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. RESULTS: A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. CONCLUSION: LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Prognostic Factors for Lymph Node Metastases in pT1 Colorectal Cancer Differ According to Tumor Morphology: A Nationwide Cohort Study.

OBJECTIVE: To investigate whether there is a differential impact of histopathological risk factors for lymph node metastases (LNM) in pedunculated and nonpedunculated pT1 colorectal cancers (CRC). BACKGROUND: Tumor budding, lymphovascular invasion (LVI), and venous invasion (VI) are recognized risk factors for LNM in pT1 CRC. Whether the importance of these factors varies according to tumor morphology is unknown. METHODS: Patients undergoing resection with lymphadenectomy for pT1 CRC in Denmark from January 2016 to January 2019 were identified in the Danish Colorectal Cancer Database and clinicopathological data was reviewed. Prognostic factors for LNM were investigated using multivariable analyses on the cohort as a whole as well as when stratifying according to tumor morphology (pedunculated vs. nonpedunculated). RESULTS: A total of 1167 eligible patients were identified, of whom 170 had LNM (14.6%). Independent prognostic factors for LNM included LVI [odds ratio (OR)=4.26, P <0.001], VI (OR=3.42, P <0.001), tumor budding (OR=2.12, P =0.002), high tumor grade (OR=2.76, P =0.020), and age per additional year (OR=0.96, P <0.001). On subgroup analyses, LVI and VI remained independently prognostic for LNM regardless of tumor morphology. However, tumor budding was only prognostic for LNM in pedunculated tumors (OR=4.19, P <0.001), whereas age was only prognostic in nonpedunculated tumors (OR=0.61, P =0.003). CONCLUSIONS: While LVI and LI were found to be prognostic of LNM in all pT1 CRC, the prognostic value of tumor budding differs between pedunculated and nonpedunculated tumors. Thus, tumor morphology should be taken into account when considering completion surgery in patients undergoing local excision.

Do differences in surgical quality account for the higher rate of R1 margins to lymph node metastases in right- versus left-sided Stage III colon cancer: A retrospective cohort study.

AIM: Microscopically positive (R1) margins to lymph node metastases (R1LNM) are associated with poorer oncological outcomes in patients with Stage III colon cancer. R1LNM margins are more common in right-sided cancer, although the cause of this phenomenon is unknown. We sought to investigate whether differences in surgical quality account for the higher rate of R1LNM in right-sided cancers. METHOD: Patients treated for Stage III colon cancer from 1 January 2016 to 31 December 2018 were identified using the Danish national cancer registry. Indicators of surgical quality (mesocolic resection grade, median lymph node yield, and length to the distal colonic margin) were compared according to tumour site and margin status. RESULTS: In all, 1765 patients were included, 981 (55.6%) with right-sided cancers. R1LNM margins were more common in right-sided cancers (14.4% vs. 6.1%, P < 0.001). All three surgical quality indicators were higher in patients with right-sided cancers (mesocolic resection planes 81.7% vs. 69.5%, P < 0.001; median lymph node yield 28 vs. 25, P < 0.001; ≥5 cm to the distal colon margin 81.2% vs. 53.6%, P < 0.001). When stratified according to margin status, no differences in mesocolic resection planes or resectate length were noted, whilst median lymph node yield was higher in patients with R1LNM margins (29 vs. 27, P = 0.009). CONCLUSION: Surgical quality does not appear to be poorer in patients undergoing surgery for right-sided versus left-sided colon cancers in Denmark. Suboptimal surgery does not appear to be responsible for R1LNM margins, implying that these margins may be a surrogate for more aggressive biology.

The impact of subdivisions of microscopically positive (R1) margins on patterns of relapse in stage III colorectal cancer - A retrospective cohort study.

AIM: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, the impact of subdivisions of R1 margins, be they to the primary tumour (R1 tumour) or to lymph node metastases (R1LNM), on patterns of relapse is unknown. METHODS: Patients treated for stage III colorectal cancer from 01 January 2016 to 31 December 2019 in four specialist centres were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1 tumour vs. R1LNM). The primary outcomes were local recurrence-free survival (LRFS), distant metastases-free survival (DMFS) and disease-specific survival (DSS). RESULTS: A total of 1,164 patients were included, with R1 margins found in 237 (20.4%). Irrespective of tumour location, R1 tumour and R1LNM margins were independent prognostic factors for systemic relapse (R1 tumour HR 1.84, CI: 1.17-2.88, p = 0.008; R1LNM HR 1.59, CI: 1.12-2.27, p = 0.009) and disease-related death (R1 tumour HR 2.08, CI: 1.12-3.85, p = 0.020; R1LNM HR 1.84, CI: 1.12-3.02, p = 0.016). Whereas R1 tumour margins were associated with poorer 3-year LRFS in both colon and rectum cancer, R1LNM margins only reduced LRFS in patients with rectal cancer. Patterns of relapse differed between R1 subdivisions, with R1 tumour margins more likely to affect multiple anatomical sites, with a predilection for extra-hepatic/pulmonary metastases. CONCLUSION: Subdivisions of R1 margins have a distinct impact on the oncological outcomes and patterns of disease relapse in patients with stage III colorectal cancer.

The significance of subdivisions of microscopically positive (R1) margins in colorectal cancer: A retrospective study of a national cancer registry.

AIM: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, little is known of the differential impact of subdivisions of R1 margins, be they to the primary tumour (R1tumour) or to lymph node metastases/tumour deposits (R1LNM). METHODS: Patients treated for Stage III colorectal cancer from 1 January 2016 to 31 December 2019 were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1tumour vs. R1LNM). The primary outcome was overall survival. RESULTS: In all, 4186 patients were included, comprising 3012 patients with colon cancer and 1174 patients with rectal cancer. The R1 resection rates were 16.5% and 18.2% in patients with colon and rectum cancer, respectively. In colon cancers, 3-year overall survival was reduced in patients with R1LNM (65.7%, 95% CI 62.8-68.6) or R1tumour margins (51.8%, 95% CI 47.3-56.3) compared with R0 resections (80.8%, 95% CI 79.9-81.6, P < 0.001). A similar impact on survival was seen in rectal cancers (R0, 84.2%, 95% CI 82.9-85.5; R1LNM, 72.2%, 95% CI 67.8-76.6; R1tumour, 56.6%, 95% CI 50.0-63.2, P < 0.001). Margin status was independently prognostic of survival in both colon (R1tumour, hazard ratio 2.08, 95% CI 1.50-2.89, P < 0.001; R1LNM, hazard ratio 1.48, 95% CI 1.11-1.97, P = 0.008) and rectal cancers (R1tumour, hazard ratio 2.35, 95% CI 1.42-3.90, P < 0.001; R1LNM, hazard ratio 1.54, 95% CI 0.95-2.48, P = 0.077). CONCLUSION: R1 subdivisions have distinct impacts on survival in Stage III colorectal cancer. Further focused research in these patient subgroups is warranted.

Major Amputations for Extremity Soft-Tissue Sarcoma.

INTRODUCTION: With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease. PATIENTS AND METHODS: Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records. RESULTS: The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS. CONCLUSIONS: Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms.

Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis.

BACKGROUND: The current American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system does not have sufficient details to encompass the variety of soft-tissue sarcomas, and available prognostic methods need refinement. We aimed to develop and externally validate two prediction nomograms for overall survival and distant metastases in patients with soft-tissue sarcoma in their extremities. METHODS: Consecutive patients who had had an operation at the Istituto Nazionale Tumori (Milan, Italy), from Jan 1, 1994, to Dec 31, 2013, formed the development cohort. Three cohorts of patient data from the Institut Gustave Roussy (Villejuif, France; from Jan 1, 1996, to May 15, 2012), Mount Sinai Hospital (Toronto, ON, Canada; from Jan 1, 1994, to Dec 31, 2013), and the Royal Marsden Hospital (London, UK; from Jan 1, 2006, to Dec 31, 2013) formed the external validation cohorts. We developed the nomogram for overall survival using a Cox multivariable model, and a Fine and Gray multivariable model for the distant metastases nomogram. We applied a backward procedure for variables selection for both nomograms. We assessed nomogram model performance by examining overall accuracy (Brier score), calibration (calibration plots and Hosmer-Lemeshow calibration test), and discrimination (Harrell C index). We plotted decision curves to evaluate the clinical usefulness of the two nomograms. FINDINGS: 1452 patients were included in the development cohort, with 420 patients included in the French validation cohort, 1436 patients in the Canadian validation cohort, and 444 patients in the UK validation cohort. In the development cohort, 10-year overall survival was 72·9% (95% CI 70·2-75·7) and 10-year crude cumulative incidence of distant metastases was 25·0% (95% CI 22·7-27·5). For the overall survival nomogram, the variables selected applying a backward procedure in the multivariable Cox model (patient's age, tumour size, Fédération Française des Centres de Lutte Contre le Cancer [FNCLCC] grade, and histological subtype) had a significant effect on overall survival. The same variables, except for patient age, were selected for the distant metastases nomogram. In the development cohort, the Harrell C index for overall survival was 0·767 (95% CI 0·743-0·789) and for distant metastases was 0·759 (0·736-0·781). In the validation cohorts, the Harrell C index for overall survival and distant metastases were 0·698 (0·638-0·754) and 0·652 (0·605-0·699; French), 0·775 (0·754-0·796) and 0·744 (0·720-0·768; Canadian), and 0·762 (0·720-0·806) and 0·749 (0·707-0·791; UK). The two nomograms both performed well in terms of discrimination (ability to distinguish between patients who have had an event from those who have not) and calibration (accuracy of nomogram prediction) when applied to the validation cohorts. INTERPRETATION: Our nomograms are reliable prognostic methods that can be used to predict overall survival and distant metastases in patients after surgical resection of soft-tissue sarcoma of the extremities. These nomograms can be offered to clinicians to improve their abilities to assess patient prognosis, strengthen the prognosis-based decision making, enhance patient stratification, and inform patients in the clinic. FUNDING: None.

The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.

Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma.

The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ILP and, in this study, we report further improvements from combining ILP-delivered oncolytic virotherapy with radiation and surgical resection. In vitro, the combination of radiation with an oncolytic vaccinia virus (GLV-1h68) and melphalan demonstrated increased cytotoxicity in a panel of sarcoma cell lines. The effects were mediated through activation of the intrinsic apoptotic pathway. In vivo, combinations of radiation, oncolytic virotherapy and standard ILP resulted in delayed tumour growth and prolonged survival when compared with standard ILP alone. However, local disease control could only be secured when such treatment was combined with surgical resection, the timing of which was crucial in determining outcome. Combinations of oncolytic virotherapy with surgical resection and radiation have direct clinical relevance in extremity sarcoma and represent an exciting prospect for improving outcomes in this pathology.

Selective marginal resections in the management of aggressive angiomyxomas.

AIM: Aggressive angiomyxomas (AA) are rare tumors, most commonly presenting in the pelvis of women of childbearing age. This study presents the results of selective marginal resection of this disease in patients managed at a single institution. METHODS: Patients diagnosed with AA from July 2001 to July 2015 were identified from a prospectively maintained histopathology database. RESULTS: Seventeen patients were diagnosed with AA in the study period. The median age at diagnosis was 48 years. Females were more commonly affected with a M:F of 1:8.5. The most common differential diagnoses were an ischiorectal abscess or Bartholin's cyst. Fifteen cases occurred in the pelvis, with two cases at other sites. Median maximum tumor diameter was 10 cm. Of the pelvic cases, 12 were managed operatively via perineal, abdominal, or abdominoperineal approaches. Excision was performed in a marginal fashion with minimal morbidity. Local recurrence developed in 58.3% with a median local recurrence free survival of 25 months. No patients developed metastatic disease or died from disease. CONCLUSION: AA are rare tumors with a propensity for local recurrence. Atypical presentations of other perineal pathologies should prompt further investigation. Surgery should be reserved for symptomatic patients and is associated with low rates of morbidity. J. Surg. Oncol. 2016;114:828-832. © 2016 2016 Wiley Periodicals, Inc.

Neoadjuvant treatment of colorectal cancer: comprehensive review.

BACKGROUND: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. METHODS: A narrative review of the most recent relevant literature was conducted. RESULTS: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. CONCLUSION: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.

Challenges presented by complete response to immune checkpoint blockade in patients with dMMR colorectal cancer: A case report.

INTRODUCTION: Early clinical trials have demonstrated remarkable responses to immune checkpoint blockade (ICB) in patients with colorectal cancers with deficient mismatch repair (dMMR) mechanisms. The precise role immunotherapy will play in the treatment of these patients is undefined, with these agents likely to produce new challenges as well as opportunities. PRESENTATION OF CASE: A 74-year-old patient was diagnosed with a locally advanced dMMR adenocarcinoma in the transverse colon with clinical suspicion of peritoneal metastases (cT4N2M1). The burden of disease was assessed as incurable, and a referral was made for palliative oncological treatment. After 5 months of treatment with pembrolizumab, a complete radiological response in the primary tumour was seen although there was still radiological suspicion of peritoneal and lymph node metastases. The patient underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but unfortunately died 6 weeks later due to complications. Final histology of the surgical specimen showed no evidence of residual disease (ypT0N0M0). DISCUSSION: This case highlights the opportunities and challenges presented by the efficacy of ICB in dMMR colorectal cancer. These agents were able to cure a patient who had disseminated disease presumed to be incurable at the time of diagnosis. However, due to current limitations in determining the degree of response to ICB, this result could only be confirmed after major surgery, which ultimately led to the patient's death. CONCLUSION: ICB can lead to dramatic responses in patients with dMMR colorectal cancers. Major challenges remain in differentiating complete and partial responders and determining the indications for conventional surgery.

One-year outcomes following operative or non-operative management of adhesional small bowel obstruction.

BACKGROUND: A trial of initial non-operative management is recommended in stable patients with adhesional small bowel obstruction. However, recent retrospective studies have suggested that early operative management may be of benefit in reducing subsequent recurrences. This study aimed to compare recurrence rates and survival in patients with adhesional small bowel obstruction treated operatively or non-operatively. METHODS: This was a prospective cohort study conducted at six acute hospitals in Denmark, including consecutive patients admitted with adhesional small bowel obstruction over a 4-month interval. Patients were stratified into two groups according to their treatment (operative versus non-operative) and followed up for 1 year after their index admission. Primary outcomes were recurrence of small bowel obstruction and overall survival within 1 year of index admission. RESULTS: A total of 201 patients were included, 118 (58.7 per cent) of whom were treated operatively during their index admission. Patients undergoing operative treatment had significantly better 1-year recurrence-free survival compared with patients managed non-operatively (operative 92.5 per cent versus non-operative 66.6 per cent, P <0.001). However, when the length of index admission was taken into account, patients treated non-operatively spent significantly less time admitted to hospital in the first year (median 3 days non-operative versus 6 days operative, P <0.001). On multivariable analysis, operative treatment was associated with decreased risks of recurrence (HR 0.22 (95 per cent c.i. 0.10-0.48), P <0.001) but an increased all-cause mortality rate (HR 2.48 (95 per cent c.i. 1.13-5.46), P = 0.024). CONCLUSION: Operative treatment of adhesional small bowel obstruction is associated with reduced risks of recurrence but increased risk of death in the first year after admission. REGISTRATION NUMBER: NCT04750811 (http://www.clinicaltrials.gov).prior (registration date: 11 February 2021).

The current role of blood-based biomarkers in surgical decision-making in patients with localised pancreatic cancer: A systematic review.

INTRODUCTION: The role of blood-based biomarkers in surgical decision-making in patients with localised pancreatic cancer remains unclear. This review aimed to report the utility of blood-based biomarkers focusing on prediction of response to neoadjuvant therapy, prediction of surgical resectability and early relapse after surgery. MATERIALS AND METHODS: MEDLINE/PubMed, Embase and Web of Science were searched till October 2019. Studies published between January 2000 and September 2019 with a minimum of 20 patients with pancreatic adenocarcinoma, reporting the utility of at least one blood-based biomarker in predicting response to neoadjuvant therapy and predicting surgical resectability or early relapse after surgery were included. RESULTS: A total of 2604 studies were identified, of which 24 comprising of 3367 patients and 12 blood-based biomarkers were included. All included studies were observational. Levels of carbohydrate antigen (CA)19-9 were reported in the majority of the studies. Levels of CA19-9 predicted the response to neoadjuvant therapy and early relapse in 10 studies. CA125 levels above 35 U/ml were predictive of surgical irresectability in two studies. However, marked variation in both timing of sampling and cut-off values was noted between studies. CONCLUSION: Despite some evidence of potential benefit, the utility of currently available blood-based biomarkers in aiding surgical decision-making in patients undergoing potentially curative treatment for pancreatic cancer is limited by methodological heterogeneity. Standardisation of future studies may allow a more comprehensive analysis of the biomarkers described in this review.

Impact of the COVID-19 pandemic on the management of colorectal cancer in Denmark.

INTRODUCTION: The COVID-19 pandemic has had a global impact on cancer care but the extent to which this has affected the management of colorectal cancer (CRC) in different countries is unknown. CRC management in Denmark was thought to have been relatively less impacted than in other nations during the first wave of the pandemic. The aim of this study was to determine the pandemic's impact on CRC in Denmark. METHODS: The Danish national cancer registry identified patients with newly diagnosed with CRC from 1 March 2020 to 1 August 2020 (pandemic interval) and corresponding dates in 2019 (prepandemic interval). Data regarding clinicopathological demographics and perioperative outcomes were retrieved and compared between the two cohorts. RESULTS: Total CRC diagnoses (201 versus 359 per month, P = 0.008) and screening diagnoses (38 versus 80 per month, P = 0.016) were both lower in the pandemic interval. The proportions of patients presenting acutely and the stage at presentation were, however, unaffected. For those patients having surgery, both colonic and rectal cancer operations fell to about half the prepandemic levels: colon (187 (i.q.r. 183-188) to 96 (i.q.r. 94-112) per month, P = 0.032) and rectal cancers (63 (i.q.r. 59-75) to 32 (i.q.r. 28-42) per month, P = 0.008). No difference was seen in surgical practice or postoperative 30-day mortality rate (colon 2.2 versus 2.2 per cent, P = 0.983; rectal 1.0 versus 2.9 per cent, P = 0.118) between the cohorts. Treatment during the pandemic interval was not independently associated with death at 30 or 90 days. CONCLUSION: The initial wave of the COVID-19 pandemic reduced the number of new diagnoses made and number of operations but had limited impact on technique or outcomes of CRC care in Denmark.

Comparison of the 7th and 8th version of the AJCC classification system for soft tissue sarcomas of extremities and trunk in patients with localised, intermediate or high-grade disease treated at European tertiary sarcoma centres.

BACKGROUND: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not improving prognostic accuracy in comparison to the 7th version. This study aimed at investigating the prognostic accuracy of both AJCC-versions in STS-patients treated at European tertiary sarcoma centres. METHODS: 1032 patients (mean age: 60.7 ± 16.3 years; 46.0% [n = 475] females; median follow-up: 38.6 months), treated at five tertiary sarcoma centres for localised, intermediate or high-grade STS of extremities and trunk were retrospectively included. Uni- and multivariate Cox-regression models and Harrell's C-indices were calculated to analyse prognostic factors for overall survival (OS) and assess prognostic accuracy. RESULTS: In univariate analysis, prognostic accuracy for OS was comparable for both AJCC-versions (C-index: 0.620 [8th] vs. 0.614 [7th]). By adding margins, age, gender, and histology to the multivariate models, prognostic accuracy of both versions could be likewise improved (C-index: 0.714 [8th] vs. 0.705 [7th]). Moreover, tumour depth did not significantly contribute to prognostic accuracy of the 8th version's multivariate model (C-index for both models: 0.714). Stratification into four main T-stages based on tumour size only, as implemented in the 8th version, significantly improved prognostic accuracy between each category. However, T-stages as defined in the 7th version had poorer discriminatory power (C-index: 0.625 [8th] vs. 0.582 [7th]). CONCLUSION: Both AJCC-versions perform equally well regarding prognostic accuracy. Yet, simplification of the 8 th version by omitting tumour depth as T-stage-defining parameter, whilst emphasizing the importance of tumour size, should be considered advantageous.

Less is more: A systematic review and meta-analysis of the outcomes of radical versus conservative primary resection in anorectal melanoma.

INTRODUCTION: Anorectal melanoma (ARM) is a rare disease with a poor prognosis. There is no consensus as to the optimal primary surgical treatment for ARM, with advocates for both radical (abdominoperineal resection [APR]) and conservative strategies (wide local excision [WLE]). Here, we report a systematic review of studies comparing outcomes between these strategies. METHODS: Studies comparing APR with WLE in patients with ARM were included, and a systematic review using the Grading of Recommendations, Assessment, Development and Evaluation methodology was performed. Outcomes deemed critical included overall survival, disease-free survival, local recurrence and quality of life. RESULTS: Forty studies were identified, of which 27 were suitable for inclusion. Twenty-three studies compared overall survival between WLE and APR, with no difference in outcomes noted (risk ratio [RR]: 0.80, 95% confidence interval [CI]: 0.60-1.07, p = 0.13). Seven studies compared disease-free survival, with no difference in outcomes noted (RR: 1.08, 95% CI: 0.61-1.91, p = 0.79). A total of 19 studies compared local recurrence rates, with again no significant difference in outcomes noted (RR: 0.71, 95% CI: 0.44-1.14, p = 0.16). None of the studies identified reported quality of life-related outcomes. CONCLUSION: There is no evidence to suggest that a radical primary surgical strategy improves outcomes in ARM. Therefore, given the well-documented morbidity associated with APR, WLE with regular surveillance for local recurrence should be the primary strategy in most patients.