Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

Potential interplay between tumor size and vitamin D receptor (VDR) polymorphisms in breast cancer prognosis: a prospective cohort study.

PURPOSE: Vitamin D has some anticancer properties that may decrease breast cancer risk and improve prognosis. The aim was to investigate associations between four previously studied VDR SNPs (Taq1, Tru91, Bsm1, and Fok1) and prognosis in different groups of breast cancer patients. METHODS: VDR genotyping of 1,017 breast cancer patients included 2002-2012 in Lund, Sweden, was performed using Oncoarray. Follow-up was until June 30, 2019. Clinical data and patient information were collected from medical records and questionnaires. Cox regression was used for survival analyses. RESULTS: Genotype frequencies were as follows: Fok1 (AA 15.7%, AG 49.1%, GG 35.1%), Bsm1 (CC 37.2%, CT 46.1%, TT 16.7%), Tru91 (CC 77.8%, CT 20.7%, TT 1.5%), and Taq1 (AA 37.2%, AG 46.2%, GG 16.6%). During follow-up there were 195 breast cancer events. The homozygous variants of Taq1 and Bsm1 were associated with reduced risk of breast cancer events (adjusted HR = 0.59, 95% CI 0.38-0.92 for Taq1 and adjusted HR = 0.61, 95% CI 0.40-0.94 for Bsm1). The G allele of the Fok1 was associated with increased risk of breast cancer events in small tumors (pT1, adjusted HR = 1.83, 95% CI 1.04-3.23) but not in large tumors (pT2/3/4, adjusted HR = 0.80, 95% CI 0.41-1.59) with a borderline interaction (Pinteraction = 0.058). No interactions between VDR genotypes and adjuvant treatments regarding breast cancer prognosis were detected. CONCLUSION: VDR genotypes were associated with breast cancer prognosis and the association might be modified by tumor size. Further research is needed to confirm the findings and elucidate their potential clinical implications.

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer.

PURPOSE: Caveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer. METHODS: A cohort of 1017 breast cancer patients (inclusion 2002-2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments). RESULTS: Only one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86-9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24-4.04). No other genotypes or haplotypes were associated with clinical outcome. CONCLUSION: CAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.

Prognostic Significance of Sentinel Lymph Node Status in Thick Primary Melanomas (> 4 mm).

BACKGROUND: The key prognostic factors for staging patients with primary cutaneous melanoma are Breslow thickness, ulceration, and sentinel lymph node (SLN) status. The multicenter selective lymphadenectomy trial (MSLT-I) verified SLN status as the most important prognostic factor for patients with intermediate-thickness melanoma (Breslow thickness, 1-4 mm). Although most international guidelines recommend SLN biopsy (SLNB) also for patients with thick (> 4 mm, pT4) melanomas, its prognostic role has been questioned. The primary aim of this study was to establish whether SLN status is prognostic in T4 melanoma tumors. METHODS: Data for all patients with a diagnosis of primary invasive cutaneous melanoma of Breslow thickness greater than 1 mm in Sweden between 2007 and 2020 were retrieved from the Swedish Melanoma Registry, a large prospective population-based registry. A multivariable Cox proportional hazard model for melanoma-specific survival (MSS) was constructed based on Breslow thickness stratified for SLN status. RESULTS: The study enrolled 10,491 patients, 1943 of whom had a Breslow thickness greater than 4 mm (pT4). A positive SLN was found for 34% of these pT4 patients. The 5-year MSS was 71%, and the 10-year MSS was 62%. There was a statistically significant difference in MSS between the patients with a positive SLN and those with a negative SLN (hazard ratio of 2.4 (95% confidence interval CI 1.6-3.5) for stage T4a and 2.0 (95% CI 1.6-2.5) for satage T4b. CONCLUSION: Sentinel lymph node status gives important prognostic information also for patients with thick (> 4 mm) melanomas, and the authors thus recommend that clinical guidelines be updated to reflect this.

Increasing melanoma incidence and survival trend shifts with improved melanoma-specific survival between 1990 and 2020 in Sweden.

BACKGROUND: Melanoma-specific survival (MSS) is heterogenous between stages and is highly dependent on the T stage for primary localized disease. New systemic therapies for metastatic cutaneous melanoma (CM) have been introduced since 2012 in Sweden. OBJECTIVES: To analyse the incidence and MSS time trends between 1990 and 2020 in Sweden. METHODS: Nationwide, population-based and prospectively collected clinico-pathological data on invasive CM from the Swedish Melanoma Registry (SweMR) were analysed for survival trends between 1990 and 2020 using Kaplan-Meier curves and Cox proportional hazard ratios (HRs). RESULTS: In total, 77 036 primary invasive CMs were diagnosed in 70 511 patients in Sweden between 1990 and 2020. The 5-year MSS [95% confidence interval (CI)] was 88.9% (88.3-89.4) for 1990-2000, 89.2% (88.7-89.6) for 2001-2010 and 93.0% (92.7-93.9) for 2011-2020. The odds ratios for being diagnosed with nodular melanoma (vs. superficial spreading melanoma) was significantly reduced by 20% (2001-2010) and by 46% (2011-2020) vs. the reference period 1990-2000. Overall, the MSS improved over both diagnostic periods (2001-2010 and 2011-2020) vs. the reference period 1990-2000 among men and women, respectively [HRmen: 2001-2010: 0.89 (95% CI 0.82-0.96) and 2011-2020: 0.62 (95% CI 0.56-0.67); HRwomen: 2001-2010: 0.82 (95% CI 0.74-0.91) and 2011-2020: 0.62 (95% CI 0.56-0.70)]. The risk of death from CM was significantly lower in all age groups for both men and women in the most recent diagnostic period (2011-2020 vs.1990-2000). CONCLUSIONS: The results emphasize the improved MSS among men and women in Sweden. The MSS improvements, specifically for the period 2011-2020, may be correlated to the introduction of new systemic therapies and are here shown for the first time in detail for Sweden.

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study.

The prognostic impact of insulin-like growth factor binding protein 7 (IGFBP7) in breast cancer is unclear. Host factors, including lifestyle, anthropometry and metabolic profile, might influence tumor-specific IGFBP7. This study aimed to investigate whether IGFBP7 levels and messenger ribonucleic acid (mRNA) expression are associated with the patient and tumor characteristics and prognosis in breast cancer. Patients with primary breast cancer in Lund, Sweden, were included preoperatively in the study between 2002 and 2012 (n = 1018). Tumor-specific IGFBP7 protein levels were evaluated with immunohistochemistry using tissue microarrays in tumors from 878 patients. IGFBP7 mRNA expression and its corresponding clinical data were obtained from The Cancer Genome Atlas and analyzed for 809 patients. Tumor-specific IGFBP7 protein levels were categorized based on Histo 300 scores into IGFBP7low (6.2%), IGFBP7intermediate (75.7%) and IGFBP7high (18.1%). Both low IGFBP7 protein levels and mRNA expression were associated with less aggressive tumor characteristics. Overall, IGFBP7low conferred low recurrence risk. The prognostic impact of IGFBP7high varied according to any alcohol consumption and tamoxifen treatment. IGFBP7high was associated with low recurrence risk in alcohol consumers but high recurrence risk in alcohol abstainers (Pinteraction= 0.039). Moreover, the combination of IGFBP7high and estrogen receptor-positive tumors was associated with low recurrence risk only in tamoxifen-treated patients (Pinteraction= 0.029). To conclude, IGFBP7low might be a good, independent prognosticator in breast cancer. The prognostic impact of IGFBP7high depends on host factors and treatment. IGFBP7 merits further investigation to confirm whether it could be a suitable biomarker for treatment selection.

CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients.

BACKGROUND: 27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. METHODS: Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis. RESULTS: CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HRadjusted = 1.93, 95%CI = 1.26-2.97, P = 0.003; breast cancer-specific survival (BCSS), HRadjusted = 2.33, 95%CI = 1.28-4.23, P = 0.006] and among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 1.99, 95%CI = 1.24-3.21, P = 0.004; BCSS, HRadjusted = 2.78, 95%CI = 1.41-5.51, P = 0.003]. Among all patients in cohort 2 (median follow-up of 7.0 years), CYP27A1 expression was significantly associated with shorter OS and RFS in univariable analyses across the full follow-up period. However after adjusting for tumor characteristics and treatments, the association with survival after 5 years from diagnosis was non-significant among all patients [OS, HRadjusted = 1.08, 95%CI = 0.05-2.35, P = 0.83 and RFS, HRadjusted = 1.22, 95%CI = 0.68-2.18, P = 0.50] as well as among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 0.46 95% CI = 0.11-1.98, P = 0.30 and RFS, HRadjusted = 0.97 95% CI = 0.44-2.10, P = 0.93]. CONCLUSION: CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition.

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma.

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only. METHODS: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group. DISCUSSION: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM. RESULTS: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412.

Participation in a Prospective Cohort Study on Melanoma did not Affect the Incidence and Mortality of the Studied Disease.

Prospective observational studies have shown previously that study participants have lower morbidity and mortality than non-participants. The aim of the current study was to determine whether participants in a prospective cohort study on melanoma have a different incidence and mortality of melanoma compared with non-participants and the background population. Information was collected from Swedish National Registers on participants (n = 30,501) and non-participants (n = 10,499) in the "Melanoma In Southern Sweden" (MISS) study and the background population (n = 243,032). Hazard ratios were calculated for overall incidence of cancer and melanoma, and all-cause and melanoma-specific mortality, using Cox regression. Participants had a lower overall incidence of cancer and all-cause mortality than non-participants and the background population. There was no difference in incidence of melanoma or melanoma-specific characteristics between participants and the background population. In conclusion, participants in the MISS study have a slightly better general health, but are a representative sample of the population with regard to studies of melanoma risk factors.

Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition.

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

The impact of body size changes on recurrence risk depends on age and estrogen receptor status in primary breast cancer.

PURPOSE: To investigate the prognostic impact of body size changes during the first postoperative year in breast cancer. METHODS: A cohort of 1,317 primary breast cancer patients included in Sweden (2002-2014) underwent body size measurements at the preoperative and 1-year visits (n = 1,178). Landmark survival analyses were used to investigate how postoperative weight gain or loss (> 5%) or change in waist-hip ratio (WHR) categories (≤ 0.85 or > 0.85) impact prognosis. RESULTS: Median age at inclusion was 61 years and body mass index 25.1 kg/m2. After a median follow-up of 5.0 years from inclusion, 165 recurrences and 77 deaths occurred. Weight gain (17.0%) conferred over twofold recurrence risk only in patients < 50 years (Pinteraction = 0.033). Weight loss (8.6%) was only associated with a poor prognosis in patients ≥ 70 years, but not after restriction analysis. Weight change did not impact prognosis in patients 50 to < 70 years. Changes between WHR categories were associated with differential recurrence risk depending on estrogen receptor (ER) status (Pinteraction = 0.007), with higher recurrence risk in patients with ER+ tumors and lower recurrence risk with ER- tumors. CONCLUSION: Both changes in terms of weight and WHR category yielded independent prognostic information. Further research is imperative before recommending weight loss for all overweight breast cancer patients.

A Population-Based Comparison of the AJCC 7th and AJCC 8th Editions for Patients Diagnosed with Stage III Cutaneous Malignant Melanoma in Sweden.

BACKGROUND: Cutaneous melanoma is steadily increasing worldwide. The new AJCC 8th edition was recently launched and introduced several changes in melanoma staging, particularly for stage III. We conducted a population-based registry study with the purpose to evaluate the impact and prognostic accuracy of the new classification in Sweden. METHODS: Consecutive patients diagnosed with stage III melanoma between January 2005 and September 2017 were identified by the Swedish Melanoma Registry (SMR) and included for analyses. Patients with multiple primary melanomas were excluded. Patients were classified according to the AJCC 7th as well as the 8th edition. Melanoma-specific survival (MSS) was retrieved from the Swedish Cause of Death Registry. RESULTS: A total of 2067 eligible patients were identified from the SMR; 1150 patients (57%) changed stage III subgroup when reclassified according to the AJCC 8th edition. The median 5- and 10-year MSS for the whole cohort of stage III melanoma patients was 59% and 51% respectively. The MSS for substage IIIA, B, and C were all improved when patients were reclassified by using to the AJCC 8th edition. The newly defined substage IIID had the worst prognosis with a 10-year MSS of 16%. CONCLUSIONS: A high proportion of patients diagnosed with stage III melanoma in Sweden between 2005 and 2017 was restaged to another subgroup, when they were reclassified according to the AJCC 8th of staging manual. We established an improved MSS for all substages compared with the former AJCC 7th edition. This may have implications on decisions about adjuvant treatment.

Increasing preoperative body size in breast cancer patients between 2002 and 2016: implications for prognosis.

Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24-99-year-old primary breast cancer patients (n = 640) in Sweden 2002-2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002-2016 (ptrends < 0.0001). Of these, a breast volume ≥ 850 mL was associated with the strongest recurrence-risk (adjusted hazard ratio [adjHR] 1.67; 95% CI 1.17-2.39), especially combined with waist circumference ≥ 80 cm (adjHR 2.07; 95% CI 1.25-3.44), while BMI ≥ 25 kg/m2 or large waist circumference conferred almost a twofold risk for death (both Log-Rank p ≤ 0.0001). Chemotherapy seemed to counteract the negative impact of a high BMI or large waist circumference on OS. Large breast volume was the strongest predictor for recurrence in all treatment groups. In conclusion, preoperative BMI, waist circumference, and breast volume increased between 2002 and 2016. Larger body size negatively impacted breast cancer-free interval and OS. If confirmed, body measurements may help select patients requiring more individualized treatment.

Sentinel lymph node biopsy in patients with thin melanomas: Frequency and predictors of metastasis based on analysis of two large international cohorts.

BACKGROUND: Sentinel lymph node (SLN) metastasis in patients with thin melanomas (≤1 mm) is uncommon but adverse prognostic factors may indicate an increased risk. We sought to determine how often SLN biopsy (SLNB) was performed in patients with thin melanomas, establish the frequency of SLN metastasis and evaluate the predictive value of ulceration, tumor mitotic rate, and thickness for SLN involvement. METHODS: Melanoma patients with a Breslow thickness greater than or equal to 0.5 to less than or equal to 1 mm, diagnosed 2009-2016, were identified in the Swedish Melanoma Register (SMR) and the Melanoma Institute Australia (MIA) Database. RESULTS: In total 8165 patients were included from the SMR and 1603 from MIA. SLNB was performed in 9.5% and 16.2% of patients, respectively. Corresponding figures for T1b (American Joint Committee on Cancer [AJCC] 7th Edition) were 19.5% and 24.6%. The SLN positivity rate were 4.4% (Sweden) and 5.8% (MIA). SLN metastasis was more frequent in tumors with ulceration, mitoses, and Breslow thickness greater than or equal to 0.9 mm but none were statistically significant. Younger age was identified as a significant risk factor for SLN positivity at MIA. CONCLUSIONS: A minority of patients with thin melanomas had SLNB performed and the SLN positivity rate was low. This study did not confirm tumor ulceration, mitoses, or thickness as statistically significant predictors for SLN metastasis.

Long-term follow-up for adhesive small bowel obstruction after open versus laparoscopic surgery for suspected appendicitis.

OBJECTIVE: The aim of the present study was to compare the frequency of readmissions due to small bowel obstruction (SBO) after open versus laparoscopic surgery performed for suspected acute appendicitis. BACKGROUND: Appendicitis is a common disease, with a lifetime risk of approximately 7%. Appendectomy is the treatment of choice for most patients. Postoperative adhesions are common after abdominal surgery, including appendectomy. MATERIALS AND METHODS: Consecutive patients, 16 years or older, operated on because of suspected appendicitis at 2 university hospitals between 1992 and 2007 were included. The prime approach was open at one hospital and laparoscopic at the other hospital. Open and laparoscopic procedures were compared retrospectively, reviewing the patients' charts until the middle of 2012. Hospitalization for SBO after index surgery was registered. RESULTS: A total of 2333 patients in the open group and 2372 patients in the laparoscopic group were included. The frequency of hospitalization for SBO was low in both groups, although a difference between the groups was identified (1.0% in the open group and 0.4% in the laparoscopic group) (P = 0.015). CONCLUSIONS: Hospitalization due to SBO, between open and laparoscopic procedures, in patients operated on because of suspected appendicitis demonstrated a significant difference, favoring the laparoscopic approach. The frequency of SBO after the index surgery was, though, low in both groups.