Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

Outcome of microscopically non-radical oesophagectomy for oesophageal and oesophagogastric junctional cancer: nationwide cohort study.

BACKGROUND: Microscopically non-radical (R1) oesophageal cancer resection has been associated with worse survival. The aim of this study was to identify risk factors for R1 resection and to investigate how this affects long-term survival. METHODS: The Swedish National Register for Oesophageal and Gastric Cancer was used to identify all patients who underwent oesophageal cancer resection with curative intent between 2006 and 2017. Risk factors for R1 resection were assessed by multivariable logistic regression analysis, and factors predicting 5-year survival identified by multivariable Cox regression. RESULTS: The study included 1460 patients. Surgical margins were involved microscopically in 142 patients (9.7 per cent). The circumferential resection margin was involved in 114 (7.8 per cent), the proximal margin in 53 (3.6 per cent), and the distal margin in 29 (2.0 per cent). In 30 specimens (2.1 per cent), two or all three margins were involved. Independent risk factors for R1 resection were male sex, low BMI, absence of neoadjuvant treatments, and clinical T4 disease. The 5-year survival rate for the entire cohort was 42.2 per cent, but only 18.0 per cent for those who had an R1 resection. Independent risk factors for death within 5 years of resection were male sex, age above 60 years, normal BMI, ASA fitness grade III, intermediate-level education, R1 resection (hazard ratio 1.80, 95 per cent c.i. 1.40 to 2.32), clinical T3 disease, and clinical lymph node metastasis. CONCLUSION: R1 resection is common and predicts poor 5-year survival. Absence of neoadjuvant treatment is a risk factor for R1 resection.

Does the Introduction of Laparoscopic Distal Pancreatectomy Jeopardize Patient Safety and Well-Being?

BACKGROUND/PURPOSE: Despite retrospective data indicating short-term superiority for laparoscopic distal pancreatectomy compared to open distal pancreatectomy, the implementation of the procedure has been slow. The aim of this study was to investigate whether patients operated with laparoscopic distal pancreatectomy during the early phase of introduction are at higher risk for complications than patients operated with open distal pancreatectomy. METHODS: A retrospective single-center analysis of patients operated with laparoscopic distal pancreatectomy (n = 37) from the introduction of the procedure and comparison regarding demographic data, preoperative data, operative factors, and postoperative outcomes to patients operated with open distal pancreatectomy was done. RESULTS: Operation duration shortened (195 vs 143 min, p = 0.04) and severe complications reduced (37% vs 6%, p = 0.02) significantly in the laparoscopic distal pancreatectomy group between the first half of the study and the second half. Blood loss was significantly (p < 0.001) lower in the laparoscopic distal pancreatectomy group (75 mL) than in the open distal pancreatectomy group (550 mL), while complication rate and hospital stay as well as the percentage of radical resections were the same. CONCLUSION: Laparoscopic distal pancreatectomy can be introduced without jeopardizing patient safety and well-being during the early learning curve. The procedures should be compared in a prospective randomized manner.

Incidence of and potential risk factors for gallstone disease in a general population sample.

BACKGROUND: Several epidemiological studies have been published, but there are few reports on relations between gallstone incidence, symptomatology and risk factors. METHODS: Of 621 randomly selected individuals aged 35-85 years in a general population who had been screened previously with ultrasonography and found to have no gallbladder stones, 503 (81.0 per cent) were re-examined after a minimum interval of 5 years. At baseline and re-examination, heredity for gallstone disease was explored and body mass index, digestive symptoms including abdominal pain, quality of life, alcohol and smoking habits, use of non-steroidal anti-inflammatory drugs and oestrogen, parity and blood lipid levels were recorded. RESULTS: Forty-two (8.3 per cent) of the 503 subjects developed stones. Subjects were followed for a total of 3025.8 person-years, yielding an incidence for newly developed gallstones of 1.39 per 100 person-years. A positive association for gallstone development was found only for length of follow-up and plasma low-density lipoprotein-cholesterol levels at baseline. Weekly alcohol consumption was inversely related to gallstone development. CONCLUSION: The incidence of gallstones in this population was 1.39 per 100 person-years. Gallstone development was related to length of follow-up and LDL-cholesterol levels, and inversely related to alcohol consumption.

Defined indications for elective cholecystectomy for gallstone disease.

BACKGROUND: This study examined symptomatology and quality of life following elective cholecystectomy for symptomatic gallstone disease with defined indications for surgery. METHODS: In this prospective study of 200 consecutive patients (161 women; median age 46.5 (range 24-79) years), strict indications for elective cholecystectomy were stipulated. Digestive symptoms and quality of life were recorded with a self-administered questionnaire before and at 3 and 12 months after surgery. RESULTS: Of 149 patients who experienced abdominal pain with typical location before surgery, 136 (91.3 per cent) reported total remission or reduced frequency of that type of pain 12 months later. Of 35 patients who reported atypical or multiple pain location before operation, 27 (77 per cent) experienced reduced frequency or disappearance of that type of pain. Frequency of pain episodes, atypical or multiple pain location, specific food intolerance and frequency of disturbing abdominal gas at baseline correlated positively with the frequency of abdominal pain episodes at 12 months after surgery. There was a tendency towards an inverse relation to age. CONCLUSION: The frequency of persistent abdominal pain after elective cholecystectomy was low among patients with typical pain location before surgery. Atypical pain location, and frequent pain episodes before operation significantly reduced the chance of becoming pain-free.

Development of symptoms and complications in individuals with asymptomatic gallstones.

BACKGROUND: Gallbladder stones are common in the developed world. Complications of gallstones contribute substantially to healthcare costs and may be life threatening. The identification of individuals likely to develop complications would be of benefit in clinical practice as elective cholecystectomy could then be performed. METHODS: Seven hundred and thirty-nine subjects aged 35-85 years from the general population were screened for gallbladder problems by ultrasonography and questionnaire assessment of putative risk factors and digestive symptoms. Gallstones, cholesterolosis or sludge in the gallbladder were diagnosed in 123 (16.3 per cent) of 739 subjects, 120 of whom were followed for a median of 87 (range 3-146) months to May 2003 or until treatment was required. RESULTS: Fourteen patients were admitted to hospital and treated for gallstone-related complications or symptoms. The cumulative risk of being treated during the first 5 years after detection of asymptomatic gallstones was 7.6 per cent and there was no indication of this risk levelling off. There were no significant differences between treated and untreated subjects with regard to digestive symptoms or any of the risk factors monitored at the initial screening, although treated subjects were significantly younger than those who were not treated. CONCLUSION: Nearly one in ten individuals with asymptomatic gallbladder stones in the general population may be expected to develop symptoms or complications that require treatment within 5 years. Age may be inversely related to the incidence of complications.

Prevalence of gallstone disease in a Swedish population sample. Relations to occupation, childbirth, health status, life style, medications, and blood lipids.

BACKGROUND: There are only a few Swedish studies on the prevalence of gallstone disease in selected age groups, and none including possible risk factors. METHODS: Of a population sample of 1200 individuals (age, 35-85 years), 857 participated in the study. The study subjects were asked to answer a questionnaire about potential risk factors (occupation, childbirth, life style, and so forth), symptoms, and quality of life. Cholecystectomy had previously been done in 115 subjects, leaving 742 for ultrasound examination of the gallbladder. RESULTS: The prevalence of gallstone disease increased with age, and at 75 years or more, 53% of the women and 32% of the men either had gallstones or had previously undergone cholecystectomy (32% and 13%, respectively). When comparing subjects with and without gallstones, there were no differences with regard to any variable, including blood lipid levels. The odds ratio of previous cholecystectomy was increased in subjects with an occupation requiring no specific education and reduced in subjects using wine or spirits every week. The odds ratio of abdominal pain was increased after previous cholecystectomy. Women in this group also experienced a lower quality of life. CONCLUSIONS: The age and sex distribution of gallstone disease was in the order of the magnitude seen in other Scandinavian countries. None of the studied variables differed between subjects with and without gallstones. Subjects previously operated on with cholecystectomy did worse with regard to symptoms and quality of life.