Epstein-Barr Virus and Clinico-Endoscopic Characteristics of Gastric Remnant Cancers Compared to Proximal Non-Remnant Cancers: A Population-Based Study.

Epstein-Barr virus (EBV) is associated with 5-10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001-2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7-68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC.

Early Gastric Cancers in Central Norway 2001 to 2016-A Population-Based Study.

Early gastric cancers (EGCs) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases and constitute only a minor proportion of gastric cancer in Western countries. We aimed to characterize EGCs and assess the survival of EGC in Central Norway during 2001-2016. A retrospective population-based study on 1205 patients with gastric cancer was performed. At the time, surgical resection was the standard treatment, and 88 (7.3%) EGCs were identified. Histopathological specimens were re-examined, and the eCura score and survival were evaluated. The number of gastric cancers declined (p = 0.010), but the relative proportion of EGC was unchanged during the study period. EGCs were more often of the Lauren intestinal type (p < 0.001) compared with controls. A significant proportion (9.4%, n = 5) of the patients with a low-risk eCura had lymph node metastases, whereas further exclusion of tumors with histological ulceration or SM2 invasion identified an N0 cohort. The median survival for EGC patients was 117.1 months (95% CI 99.8-134.3) and the 5-year overall survival was 75%. Twelve deaths were cancer-related, either due to postoperative complications (5.7%, n = 5) or cancer recurrence (8%, n = 7). In conclusion, EGCs constituted a minor but constant proportion of gastric cancers. eCura alone was insufficient in predicting patients with pN0 disease.

Gastric remnant cancer and long-term survival in Central Norway 2001 to 2016 - A population-based study.

INTRODUCTION: Gastric remnant cancer (GRC) has been defined as a distinct clinical entity and is reported to account for 1-8% of all gastric cancers. We aimed to characterize GRC patients and assess survival in a Western population. METHODS: Retrospective population-based cohort study including 1217 patients diagnosed with gastric adenocarcinoma in Central Norway 2001-2016. GRCs (n = 78) defined as adenocarcinomas arising in the residual stomach after distal gastrectomy were compared to non-GRC (n = 1139) and to proximal non-GRC (n = 595). RESULTS: 78 (6.4 %) gastric cancers were GRC. The annual number and proportion of GRC declined during the study period (p = 0.003). Median latency from distal gastrectomy to GRC diagnosis was 37.6 years (15.7-68.0) and previous Billroth II reconstruction was most common (87.7%). Compared to controls, GRC patients were more frequently males (83.3%), diagnosed in earlier TNM stages and were older at diagnosis. A smaller proportion of GRC patients received perioperative or palliative chemotherapy, but the R0/R1resection rate of 41.0% was no different from non-GRC patients. Overall median survival for GRC patients irrespective of treatment was 7.0 months, which did not differ from non-GRCs or proximal non-GRC. In multivariate analyses TNM stage and age were independently associated with mortality, whereas GRC per se was not. CONCLUSIONS: Numbers of GRCs declined during the study period, but the latency between distal gastrectomy and GRC diagnosis was long. GRC patients were more frequently male and older than other gastric cancer patients. GRC was not independently associated with survival after adjusting for TNM stage and tumor location.

Cumulative incidence of first recurrence after curative treatment of stage I-III colorectal cancer. Competing risk analyses of temporal and anatomic patterns.

BACKGROUND: Updated knowledge about the rates of recurrence and time to recurrence following curative treatment of colorectal cancer is essential to secure better patient information on prognosis, to serve as a premise in the discussion on adjuvant chemotherapy, and help to properly scale the intensity and length of follow-up. METHODS: This is a population-based study investigating aspects on first recurrence after radical treatment of clinical stages I-III of colorectal cancer in Central-Norway during 2001-2015. To reveal any time-trends, data were stratified by the time periods 2001-2005, 2006-2010 and 2011-2015. The cumulative incidence of first recurrence was calculated, treating death of unrelated causes as a competing event. Multivariable Cox analyses were done to calculate cause specific hazard ratios (HR) for risk of recurrence. RESULTS: At a minimum follow-up of six years, a first recurrence was detected in 1,113/5,556 patients at risk (20.0%). The recurrence rate was reduced from 23.6% in the first time period, through 20.0% in the second, and to 17.2% in the last, p < 0.001. The reduction applied to all tumor locations, to pathological disease stages II and III, to both gender, across different tumor differentiations, and to both elective and emergency surgery. In multivariable analyses time period, gender, disease stage, and tumor differentiation were significant determinants for risk of recurrence. CONCLUSIONS: The rate of first recurrence after curative surgery for colorectal cancer was substantially reduced from 2001 to 2015. The reason for the reduction could not be attributed to a single factor only. A combined effect of several incremental improvements, such as an increased use of preoperative radiation for rectal cancers, improved adjuvant chemotherapy for colon cancer, and a reduced proportion of emergency surgery, is suggested.

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. METHODS: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. RESULTS: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. CONCLUSIONS: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

Gastric Cancers Missed at Upper Endoscopy in Central Norway 2007 to 2016-A Population-Based Study.

BACKGROUND: The rates of missed gastric cancers (MGC) at upper endoscopy (UE) has been reported at 5-10% in Western countries. We aimed to calculate the rate of MGC and identify factors associated with MGC. METHODS: Retrospective population-based cohort study including 730 patients diagnosed with gastric adenocarcinoma in Central Norway 2007-2016. MGCs were incident gastric adenocarcinomas diagnosed 6-36 months after a previous UE. Factors associated with MGC were examined. Definitely missed (UE 6-12 months prior) and potentially missed (UE 12-36 months prior) MGCs were compared. RESULTS: Sixty-seven (9.2%) of 730 gastric cancers were MGC. MGC were associated with localization (p = 0.009) and more frequent in the corpus, Lauren's histological type (p = 0.028) and diffuse type more prevalent, and previous Billroth 2-operation (14.9% vs. 4.7%, p = 0.001). MGCs were diagnosed at earlier stages (p = 0.037). An ulceration was more common in patients with definitely missed than potentially MGC (40.9% vs. 17.8%, p = 0.041). CONCLUSIONS: MGC accounted for 9.2% of gastric cancers in Central Norway. MGC were associated with localization in the corpus, Lauren´s diffuse type and previous Billroth-2-operation. Intensified follow-up and adequate biopsy sampling of patients with gastric ulcerations could reduce the rate of missed gastric cancers.

Simultaneous Resection of Primary Colorectal Cancer and Synchronous Liver Metastases: Contemporary Practice, Evidence and Knowledge Gaps.

The timing of surgical resection of synchronous liver metastases from colorectal cancer has been debated for decades. Several strategies have been proposed, but high-level evidence remains scarce. Simultaneous resection of the primary tumour and liver metastases has been described in numerous retrospective audits and meta-analyses. The potential benefits of simultaneous resections are the eradication of the tumour burden in one procedure, overall shorter procedure time, reduced hospital stay with the likely benefits on quality of life and an expected reduction in the use of health care services compared to staged procedures. However, concerns about accumulating complications and oncological outcomes remain and the optimal selection criteria for whom simultaneous resections are beneficial remains undetermined. Based on the current level of evidence, simultaneous resection should be restricted to patients with a limited liver tumour burden. More high-level evidence studies are needed to evaluate the quality of life, complication burden, oncological outcomes, as well as overall health care implications for simultaneous resections.

Impact of increased resection rates and a liver parenchyma sparing strategy on long-term survival after surgery for colorectal liver metastases. A population-based study.

Background and aims: Expanded criteria for resection of colorectal liver metastases (CRLM) have led to a more aggressive surgical attitude. The aim is to evaluate any impact of expanded criteria on perioperative mortality and long-term survival. Materials and methods: A population based study from 2001 to 2015 for patients undergoing surgery for CRLM. The cohort was divided into three 5-year periods. Results: A total of 341 patients underwent resection of CRLM. Relative to the number of colorectal primaries, patients resected for CRLM increased from 82/2520 (3.3%) in 2001-2005 to 151/3071 (4.9%) in 2011-2015 (p = .007). The proportion of patients who underwent formal resections declined from 62% to 21%. There was a substantial increase in resections of synchronous liver metastases, portal vein embolizations, two-stage resections, and the share of octogenarians who underwent resection. The proportion of patients undergoing reresections of new liver recurrences increased from 6% to 24%. The 90-d postoperative mortality for 2001-2005, 2006-2010, and 2011-2015 were 7.9%, 0.8%, and 2.0%, respectively. The median overall survival was 47 months during the two first periods, for the last period not reached. The 5-year overall survival remained at 40% from 2001 to 2010, and estimated at 55.2% from 2011 to 2015. The 5-year disease-free survival was well above 30%. The 5-year overall survival following liver reresection was 52.6%. Conclusion: Postoperative mortality remained at approximately 2%, and the 5-year overall survival at 40% in the first 10 years, but increased to 55% in the last 5 years under study, despite a marked increase in resection rates.

Perioperative chemotherapy for resectable gastric cancer - what is the evidence?

The UK MAGIC trial published in 2006 was the first RCT to identify improved long-term survival rates using preoperative chemotherapy for resectable gastric or gastroesophageal cancer. Overnight, the treatment regimen impacted European guidelines. However, the majority of patients underwent limited lymph node dissection, and analyses of the rates of curative resection, downsizing and downstaging were not by intention to treat, rightfully raising concerns about their validity. For the subset of true gastric cancers, meta-analyses may even question the claims of improved long-term survival rates by present-day regimens. A rhetorical question can be posed as to whether downstaging and improved survival rates by preoperative (radio)-chemotherapy for cancers of the distal esophagus or gastric cardia, has confounded our conclusions on the (lack of) effect of present-day regimens of perioperative chemotherapy for true gastric cancers, let alone in a situation with proper lymph node dissection. At present, a plea can be made to move one step back and revert to an RCT with a surgery alone arm. Inclusion criteria and analyses of future RCTs must stratify on tumor location and the Lauren type and embrace the newly developed scheme of sub-classification of gastric cancers based on extensive molecular profiling as reported in the seminal Cancer Genome Atlas Study.

A population-based study on incidence rates, Lauren distribution, stage distribution, treatment, and long-term outcomes for gastric adenocarcinoma in Central Norway 2001-2011.

BACKGROUND: Population-based studies for gastric adenocarcinoma are scarce, particularly studies conducted within a defined geographical area with publicly available censuses that allow incidence rates to be calculated. MATERIAL AND METHODS: Population-based study in Central Norway from 2001 to 2011, covering a population of 636 000-680 000, respectively. Patients were identified through the Cancer Registry of Norway and the Norwegian Patient Register, and were characterized by data from individual electronic patient records. Outcomes were compared across the early and the late half of the study period. RESULTS: A total of 878 patients were identified with a median age of 76.2 years. The male to female ratio was 1.72. Annual world age-standardized incidence was 8.0/105 and 3.6/105, respectively. The Lauren diffuse type was significantly more frequent among patients below 60 years, among females and for non-cardia cancers, compared to their counterparts (p < .001). The Lauren mixed type had a stable proportion of around 13% irrespective of age, sex or tumor location. Early gastric cancers (EGC) represented 8.3% of the cases, whereas 44% of all patients were diagnosed with metastatic disease. In males, the proportion of cardia cancers increased from 29.7% to 39.1% during the study period (p = .005). The five-year overall survival was 16%, and was substantially better for the Lauren intestinal type compared to the diffuse type, log-rank p = .003. The R0-R1 resection rate was 39%, with a corresponding five-year survival of 40.9%. CONCLUSIONS: This study provides population-derived data lacking in hospital-based studies. Lauren categories with epidemiological aspects and clinical outcomes are displayed. Gastric cancer was associated with a dismal prognosis. Few patients had EGC and close to 50% had metastatic disease. Many were too old or frail to be considered for surgery.