Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

Sexual Health Needs: How Do Breast Cancer Patients and Their Partners Want Information?

It is well known that breast cancer treatment can affect sexuality. This survey evaluated the needs of breast cancer patients and partners regarding sexual care. The majority of patients (80.4%) and partners (73.7%) did not receive any information regarding sexuality. Although only a quarter of all respondents reported a direct need for information regarding sexuality, most valued an opportunity to discuss sexuality. The nurse practitioner was the most preferable care provider to provide information about sexuality, supported by a brochure or website. Patients considered during treatment as most suitable timing of discussing sexuality, and partners before the start of treatment.

Volume- or outcome-based referral to improve quality of care for esophageal cancer surgery in The Netherlands.

Recently, in The Netherlands esophageal resections for cancer are banned from hospitals with an annual volume less than 10. In this study we evaluate the validity of this specific volume cut-off, based on a review of the literature and an analysis of the available data on esophagectomies in our country. In addition, we compare the expected benefits of volume-based referral to the results of a regional centralization process based on differences in outcome (outcome-based referral).

[One hundred years of the Association of Surgeons in the Netherlands. VI. The training]. / Honderd jaar Nederlandse Vereniging voor Heelkunde. VI. De opleiding.

Over the last 25 years the organisation and content of the residency training program for general surgeons have been adapted to meet the needs of changing surgical practice. Recently more profound changes have been dictated by the Dutch Working Hours Act, which has strictly limited the working hours of resident physicians. With this the emphasis will be on improving theoretical and practical training methods. Because of the limiting working hours resident physicians will have a smaller role in patient care. These changes will require a huge effort from both the teaching surgeons and the resident physicians, as well as substantial financial investments from the government and healthcare providers.

The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs.

Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of approximately 25% of the normal mass islets--as compared to 30 controls. A similar posttransplant reduction to approximately 25% of the insulin secretory capacity as assessed by intravenous arginine stimulation during 35 mM glucose clamps, mirrored the reduction of the islet mass. Postprandially, in contrast, the insulin response had increased to 140% in the islet recipients--with a concomitant rise of glycemia to approximately 8.5 mM. Posttransplant, the insulin secretory capacity correlated both with the index of insulin action (which averaged 55% of the normal value) as assessed by euglycemic hyperinsulinemic clamps, and--inverse--with the postprandial glucose excursions. Because insulin action did not correlate with postprandial glucose, the insulin secretory capacity appears to be the primary determinant of the impaired glucose tolerance. Marked postprandial hyperglucagonemia, and a virtually absent pancreatic polypeptide response in the grafted animals, may also have contributed to the impaired glucose tolerance. Posttransplant, infusion of a physiological dose of the gut hormone glucagon-like peptide-1 during 8.5 mM glucose clamps--mimicking the postprandial glycemia--potentiated glucose-stimulated insulin 175%. Thus, after transplantation of a suboptimal islet mass, postprandial glucose excursions are restrained by hyperglycemic potentiation of the entero-insular axis, which may account for the difference in the insulin response to the intravenous and oral challenges. Because, the insulin secretory capacity reflects the islet mass and appears to be the major determinant of glucoregulation, transplantation of a larger islet mass may allow near-normal glycemic control.

Glucoregulation after canine islet transplantation: contribution of insulin secretory capacity, insulin action, and the entero-insular axis.

The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated. We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal stimulation at 6-9 mo after intrasplenic islet autotransplantation in 8 dogs, as compared with 30 controls. The enteroinsular axis in the recipients was examined by infusion of porcine glucose-dependent insulinotropic polypeptide (GIP) and human glucagon-like peptide-1 (GLP-1) (7-36 amide) under 8.5-mM glycemic clamp conditions in order to mimic the postprandial glycemia after transplantation. The grafts comprised 25% of the native islet mass, and the ISC likewise averaged 25% of the control value. The postprandial insulin response, in contrast, had increased to 140% after transplantation--albeit with a concomitant glucose excursion to approximately 8.5 mM. Insulin action declined on average by 45% posttransplant. The ISC correlated both with the postprandial glucose excursion and insulin action in the grafted dogs. Insulin action did not correlate with the postprandial glucose excursion. Infusion of GIP had no effect, but GLP-1 nearly doubled glucose-stimulated insulin. Thus, a hyperglycemia-enhanced insulinotropic effect of GLP-1, and perhaps other gut hormones, may account for the difference in the insulin response to the intravenous and oral challenges. Because the ISC reflects the engrafted islet mass and appears to be the primary determinant of glucose tolerance, transplantation of higher islet doses should allow prolonged near-normal glucoregulation--at least in the autotransplant setting.

Function and survival of intrasplenic islet autografts in dogs.

Successful transplantation of isolated islets of Langerhans has been reported in large mammals, including man, but metabolic control has not been well-established. We studied the glucose and islet hormone response to fasting, i.v. glucose bolus infusion, i.v. arginine bolus infusion during a 35-mmol/l hyperglycaemic clamp, mixed meals, and i.v. insulin-induced hypoglycaemia up to 3 years after intrasplenic islet autotransplantation in six pancreatectomised dogs. The individual postprandial insulinogenic index (ratio of 2-h postprandial insulin to glucose levels) at 1 month post-transplant, predicted (r = 0.99) the time to functional graft failure (6-175 weeks). Metabolic studies at 6 months post-transplant in four dogs demonstrated normal fasting glucose and hormone levels, except for reduced pancreatic polypeptide levels. Intravenous glucose and arginine-stimulated insulin were reduced to 15% of preoperative values. In contrast, postprandial normoinsulinaemia was observed--albeit with moderate hyperglycaemia (approximately 10 mmol/l). Postprandial glucagon and glucose-dependent insulinotropic polypeptide (GIP) had increased. Comparison of the post-transplant insulin responses to a meal and to intravenous challenges demonstrated maximal stimulation of the graft by the meal. Post-transplant pancreatic polypeptide responses to a meal and i.v. arginine were severely reduced, and no pancreatic polypeptide response to i.v. insulin-induced hypoglycaemia was observed--indicating absence of cholinergic reinnervation. Thus, glucose regulation and both the insulin secretory capacity and life expectancy of islet grafts were best documented by meal testing. Tentatively, a postprandial hyperglycaemia-enhanced incretin effect of glucose-dependent insulinotropic polypeptide and other gut hormones may account for the difference in the insulin response to i.v. glucose and a meal. Aside from the reduced insulin secretory capacity, both a deranged pulsatile delivery of insulin, hyperglucagonaemia, and pancreatic polypeptide deficiency may have been conducive to glucose intolerance.

Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets.

Recent metabolic studies suggest that the incretin effect of gut hormones may account for most of the circulating insulin during mild postprandial hyperglycemia after transplantation of isolated islets. As yet, however, insulinotropic effects of pharmacological rather than physiological levels of the incretin candidates cholecystokinin-33 (CCK-33), gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) on isolated perifused islets have been reported. We examined the insulinotropic effects of these peptides during perifusion of canine isolated islets. Exploration of beta-cell sensitivity in our model with graded 0.1-10 nM doses of CCK-33 and GIP at a 7.5 mM glucose level demonstrated insulinotropic effects from the lowest level. We, therefore, focused on the (near-) physiological effects of both CCK-33 (20 pM), GIP (500 pM), and GLP-1 (100 pM) during perifusion at a 2.5, 7.5, and 10 mM glucose level. No effects of CCK-33 were observed. GIP enhanced insulin release 1.1- and 1.2-fold, at the 7.5 and 10 mM glucose level, respectively. GLP-1 stimulated insulin output from the 2.5 mM glucose level; and a maximum, 2-fold, increase of insulin output was observed from the 7.5 mM glucose level. Thus, isolated perifused islets do respond to near-physiological beta-cell stimulation with gut hormones, and both GIP and GLP-1 may contribute to a hyperglycemia-enhanced activation of the enteroinsular axis after transplantation of isolated islets.

Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation.

Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin (CCK) and intravenous bombesin-stimulated PP levels were studied in beagles at three successive intervals in a crossover design. The first was 6 wk after partial (approximately 70%) pancreatectomy with intact regular enteric exocrine drainage from the duodenal pancreatic remnant, the next was 2 wk after venous transposition with systemic delivery of pancreatic hormones, and the third was 6 wk after in situ duct obliteration of the remnant. With partial pancreatectomy, K values were modestly diminished (30%), and a concomitant reduction of second-phase intravenous glucose-stimulated insulin release was observed. Other parameters were not significantly affected. Venous transposition doubled peripheral plasma levels of insulin under all conditions. Fasting glucose, PP, and CCK levels decreased slightly. Other parameters were not affected. Duct obliteration of the systemic draining pancreatic remnants seriously impaired glucose sensitivity, resulting in a 50% reduction of K values and fasting and sustained postprandial hyperglycemia (approximately 8 mM) and a 70-50% reduction (acute and overall responses, respectively) of intravenous glucose-stimulated insulin. Fasting hormone and postprandial insulin, glucagon, and CCK levels were not affected. The postprandial PP response was severely reduced, and bombesin-stimulated PP release was abolished by duct obliteration. We conclude that histological changes associated with duct obliteration are the major determinants of glucose regulation in segmental pancreas transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Crossover study on effects of duct obliteration, celiac denervation, and autotransplantation on glucose- and meal-stimulated insulin, glucagon, and pancreatic polypeptide levels.

In segmental-pancreas transplantation the body and tail of the pancreas are used. In an experimental study in dogs, the effects of sequentially conducted removal of the right pancreatic lobe (pancreatic head), duct obliteration, celiac denervation, and autotransplantation were studied according to a crossover design. Two groups of dogs were studied. In both groups the right lobe of the pancreas was removed at primary operation, and the duct of the transected left lobe (body and tail) was injected with fibrin sealant. The left lobe was completely freed from surrounding tissue (celiac denervation) in group 1 (n = 9), and the innervation of the left lobe was left intact in group 2 (n = 8). At 12 wk, two dogs in group 1 and four dogs in group 2 underwent successful autotransplantation of the left lobe. Pancreatic hormone secretion was stimulated by intravenous glucose injection and test-meal administration before primary operation and at 11 and 18 wk thereafter. The combination of removal of the right lobe and duct obliteration led to a decrease in glucose tolerance at both stimulation tests and a decrease in peripheral insulin release after intravenous glucose injection. At test-meal administration, no change in insulin and glucagon levels was demonstrated. If celiac denervation was added, similar results were obtained based on the understanding that the peripheral insulin release after the test meal was significantly elevated. Meal-stimulated pancreatic polypeptide response was abolished in both groups. Removal of the right lobe leads to parasympathic denervation of the left lobe, and celiac denervation mainly interferes with alpha-adrenergic innervation.(ABSTRACT TRUNCATED AT 250 WORDS)