Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-determination: the Italian Road to Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) is considered the most efficient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the final part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefits of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. METHODS: An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twenty-three tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. RESULTS: Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30-59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. CONCLUSIONS: The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patients are younger, more educated, more professional, and more mobile than patients referred by other physicians. Older patients and with a longer duration of obesity are probably representative of the conservative approach to BS, often regarded as the last resort in an endless story.

Biliopancreatic Diversion (BPD), Long Common Limb Revisional Biliopancreatic Diversion (BPD + LCL-R), Roux-en-Y Gastric Bypass [RYGB] and Sleeve Gastrectomy (SG) mediate differential quantitative changes in body weight and qualitative modifications in body composition: a 5-year study.

AIMS: Bariatric surgeries induce profound weight loss (decrease in body mass index, BMI), through a decrease in fat mass (FM) and to a much lesser degree of fat-free mass (FFM). Some reports indicate that the weight which is lost after gastric bypass (RYGB) and sleeve gastrectomy (SG) is at least partially regained 2 years after surgery. Here we compare changes in BMI and body composition induced by four bariatric procedures in a 5 years follow-up study. METHODS: We analyzed retrospectively modifications in BMI, FM and FFM obtained through Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), biliopancreatic diversion (BPD) and a long common limb revisional biliopancreatic diversion (reduction of the gastric pouch and long common limb; BPD + LCL-R). Patients were evaluated at baseline and yearly for 5 years. Of the whole cohort of 565 patients, a subset of 180 patients had all yearly evaluations, while the remaining had incomplete evaluations. Setting University Hospital. RESULTS: In a total of 180 patients evaluated yearly for 5 years, decrease in BMI and FM up to 2 years was more rapid with RYGB and SG than BPD and BPD + LCL-R; with RYGB and SG both BMI and FM slightly increased in the years 3-5. At 5 years, the differences were not significant. When analysing the differences between 2 and 5 years, BPD + LCL-R showed a somewhat greater effect on BMI and FM than RYGB, BPD and SG. Superimposable results were obtained when the whole cohort of 565 patients with incomplete evaluation was considered. CONCLUSIONS: All surgeries were highly effective in reducing BMI and fat mass at around 2 years; with RYGB and SG both BMI and FM slightly increased in the years 3-5, while BPD and BPD + LCL-R showed a slight further decreases in the same time interval.

Compared with Controls, Bariatric Surgery Prevents Long-Term Mortality in Persons with Obesity Only Above Median Age of Cohorts: a Systematic Review and Meta-Analysis.

PURPOSE: Compared to medical treatment, bariatric surgery reduces long-term mortality in persons with obesity. Some studies indicate that the effect only applies to patients above median age of cohorts, not to younger patients. Our objective was to assess the role of age in the reduction of mortality (global mortality and mortality for specific causes) through bariatric surgery. MATERIALS AND METHODS: Data sources: PubMed, Cochrane Library, MEDLINE, and Embase. STUDY SELECTION: studies reporting mortality in relation to median age of patients. DATA EXTRACTION AND SYNTHESIS: pooled random effects of estimates of the risk of mortality in participants undergoing surgery compared with controls, as function of median age. RESULTS: Mortality was lower in patients undergoing surgery than in controls (OR = 0.29, 95% CI 0.17-0.49). Below median age, the difference between surgery patients and controls was nonsignificant (OR = 0.78, 95% CI 0.57-1.06). Above median age, the difference was significant (OR = 0.23, 95% CI 0.12-0.44). In a subset of 5 studies, deaths due to various causes were less, and external causes-related deaths were more frequent in surgery than in controls. Below median age, deaths due to CVD were less frequent in surgery than in controls. Above median age, total deaths and deaths due to various causes (cardiovascular, diabetes, cancer, and other causes) were less in surgery than in controls. Publication bias was absent. CONCLUSION: Compared with controls, bariatric surgery reduces long-term global mortality only above median age, not below median age. Also mortality due to specific causes is mainly reduced in persons above median age.

Bariatric surgery, compared to medical treatment, reduces morbidity at all ages but does not reduce mortality in patients aged < 43 years, especially if diabetes mellitus is present: a post hoc analysis of two retrospective cohort studies.

BACKGROUND AND AIMS: Bariatric surgery (BS) reduces long-term mortality in comparison with medical treatment of obesity. Some studies indicate that this effect is significant for patients above mean age in different cohorts, but not for younger patients. These findings raise the question whether morbid obese patients should undergo BS as soon as possible, or whether patients might undergo surgery later in their life. METHODS: We performed a post hoc analysis of two studies; we evaluated surgery-related long-term mortality in: (1) the whole cohort [857 surgery patients (163 diabetes) vs. 2086 controls (512 diabetes)]; (2) patients above mean age [> 43 years, 427 surgery patients (133 diabetes) vs. 1054 controls (392 diabetes)]; (3) patients below mean age [≤ 43 years, 432 surgery patients (30 diabetes) vs. 1032 controls (120 diabetes]. Then, we analyzed age-related long-term mortality in the whole cohort, as well as in surgery patients and in controls. Finally, we analyzed incident diseases (diabetes, cardiovascular disease, and cancer) as a function of surgery versus no-surgery and of mean age. RESULTS: Surgery patients, compared with controls receiving standard medical/dietary treatment, had reduced mortality in the whole cohort (HR = 0.45, 95% CI 0.33-0.62, p = 0.001) and in the study group aged > 43 years (HR = 0.39, 95% CI 0.28-0.56, p = 0.001), but not in the study group aged ≤ 43 years (HR = 0.87, 95% CI 0.42-1.80, p = 0.711). Reduced mortality was observed in non-diabetic and diabetic patients aged > 43 years (HR = 0.37, 95% CI 0.23-0.62, p = 0.001 and HR = 0.45, 95% CI 0.27-0.74, p = 0.002, respectively) who underwent bariatric surgery. In contrast, in patients aged ≤ 43 years, no significant protective effect of bariatric surgery appeared in non-diabetic patients (HR = 0.64, 95% CI 0.24-1.71, p = 0.371), and mortality increased, almost significantly, in diabetic patients aged < 43 years (HR = 2.87, 95% CI 0.96-8.56, p = 0.058), and even more in diabetic patients aged 33-43 years; HR = 4.99, 95% CI 1.18-21.09, p = 0.029). As expected, age-related mortality was increased in the whole cohort (HR = 7.23, 95% CI 5.14-10.17, p = 0.001), in non-diabetic and diabetic controls (HR = 8.55, 95% CI 5.77-12.68, p = 0.001, and HR = 3.76, 95% CI 1.97-7.18, p = 0.001, respectively). The effect of aging was slightly reduced in surgery patients (HR = 3.76, 95% CI 1.87-7.58, p = 0.001), while it was not significant in diabetic surgery patients (HR = 0.70, 95% CI 0.26-1.90, p = 0.88), further emphasizing that diabetes per se has a strong negative effect on survival, also with concomitant bariatric surgery. In a supplementary analysis, HRs did not change when surgery and control parents were matched for the presence of diabetes. Incident diseases (cardiovascular, diabetes, and cancer) were less frequent in surgery than in control patients, irrespective of age. CONCLUSION: Bariatric surgery reduces long-term mortality in comparison with medical treatment when performed in patients aged > 43 years, but not in younger patients, where it is neutral or could even increase mortality; reduction in morbidity occurs at any age.

Long-term mortality in obese subjects undergoing malabsorptive surgery (biliopancreatic diversion and biliointestinal bypass) versus medical treatment.

BACKGROUND AND AIM: Aim of this study was to analyze long-term mortality in obese patients receiving malabsorptive bariatric surgery (BS)[biliopancreatic diversion (BPD) and biliointestinal bypass (BIBP)] in comparison to medical treatment of obesity. PATIENTS AND METHODS: Medical records of 1877 obese patients [body mass index (BMI) > 35 kg/m2, aged 18-65 years, undergoing BS (n = 472, 111 with diabetes) or non-surgical medical treatment (n = 1405, 385 with diabetes), during the period 1999-2008 (visit 1)] were collected; non-surgical patients were matched for age, sex, BMI, and blood pressure, and life status and causes of death were ascertained through December 2016. Survival was compared across surgery patients and non-surgical patients using Kaplan-Meier plots and Cox regression analyses. RESULTS: Observation period was 12.1 ± 3.41 years (mean ± SD). Compared to non-surgical patients, BS patients had reduced all-cause mortality (34/472 (7.2%) vs 181/1,405 (12.9%) patients, χ2 = 11.25, p = 0.001; HR = 0.64, 95% C.I. 0.43-0.93, p = 0.019). Cardiovascular and cancer causes of death were significantly less frequent in surgery vs no-surgery (HR = 0.26, 95% C.I. 0.09-0.72, p = 0.003; HR = 0.21, 95% C.I. 0.09-0.45, p < 0.001, respectively). CONCLUSION: Patients who have undergone BPD and BIBP have lower long-term all-cause, cardiovascular-caused and cancer-caused mortality compared to non-surgical medical weight-loss treatment patients. Malabsorptive bariatric surgery significantly reduces long-term mortality in severely obese patients.

Incidence of Diabetes Mellitus, Cardiovascular Diseases, and Cancer in Patients Undergoing Malabsorptive Surgery (Biliopancreatic Diversion and Biliointestinal Bypass) vs Medical Treatment.

BACKGROUND AND AIMS: Bariatric surgeries such as gastric banding (LAGB), gastric bypass (RYGB), vertical banded gastroplasty (VBG), and sleeve gastrectomy (LSG) decrease body weight in morbid obesity, leading to the resolution of coexisting diabetes mellitus and arterial hypertension in the majority of cases as well as improvements of renal function and liver steatosis. BS (LAGB, RYGB, VBG, and LSG) also reduce incident cases of diabetes, of cardiovascular diseases, and of cancer; these therapeutic and preventive effects on comorbidities of obesity have not been analyzed for malabsorptive surgeries such as biliopancreatic diversion (BPD) or biliointestinal bypass (BIBP). The aim of this study was to analyze the incidence of comorbidities, i.e., diabetes, cardiovascular diseases, and cancer, in obese subjects undergoing BPD and BIBP, in comparison with standard medical treatment of obesity. PATIENTS AND METHODS: Medical records of 1983 obese patients (body mass index (BMI) > 35 kg/m2, aged 18-65 years, undergoing surgery (n = 472, of which 111 with diabetes) or medical treatment (n = 1511, of which 422 with diabetes), during the period 1999-2008 (visit 1)) were collected; incident cases of comorbidities were ascertained through December 31, 2016. RESULTS: Observation period was 12.0 ± 3.48 years (mean ± SD). Compared to non-surgical patients matched for age, body mass index, and blood pressure, malabsorptive surgeries were associated with reduced new incident cases of diabetes (p = 0.001), cardiovascular diseases (p = 0.001), hyperlipidemia (p = 0.001), oculopathy (p = 0.021), and cancer (p = 0.001). The preventive effect of BS was similar in both nondiabetic and diabetic patients for cardiovascular diseases and hyperlipidemia (both p = 0.001). The preventive effect was significant in nondiabetic subjects for coronary heart disease and for cancer, not significant in diabetic subjects. CONCLUSION: Patients undergoing malabsorptive bariatric surgery show less incident cases of diabetes, cardiovascular diseases, hyperlipidemia, oculopathy, and cancer than controls receiving medical treatment.

Intranasal glucagon for hypoglycaemia in diabetic patients. An old dream is becoming reality?

In 1983 it was shown that glucagon administered intranasally (IN) was absorbed through the nasal mucosa and increased blood glucose in healthy subjects. Shortly thereafter, it was shown that IN glucagon counteracts with hypoglycaemia in insulin-treated diabetic patients. In spite of this evidence, IN glucagon was not developed by any pharmaceutical company before 2010, when renewed interest led to intensive evaluation of a possible remedy for hypoglycaemia in insulin-treated diabetic adults and children. IN glucagon is now being developed as a needle-free device that delivers glucagon powder for treatment of severe hypoglycaemia; the ease of using this device stands in stark contrast to the difficulties encountered in use of the current intramuscular glucagon emergency kits. Studies have demonstrated the efficacy, safety and ease-of-use of this IN glucagon preparation, and suggest IN glucagon as a promising alternative to injectable glucagon for treating severe hypoglycaemia in children and adults who use insulin. This would meet the unmet medical need for an easily administered glucagon preparation.

Revision of Biliopancreatic Diversion for Side Effects or Insufficient Weight Loss: Codification of a New Procedure.

PURPOSE: Addressing the problem of proctologic sequelae after Scopinaro's classical BPD, we elongated the common limb from 50 to 200 cm at the expense of the alimentary limb and simultaneously, with the aim of avoiding weight regain, reduced the gastric pouch from 500 to 40 ml. After increased experience with the new procedure, we observed a favourable tendency towards further weight loss. Thus, we subsequently extended the indication to the procedure to patients with unsatisfactory weight loss after Scopinaro's classical BPD (SBPD). METHODS: We retrospectively reviewed our clinical experience with the new procedure. RESULTS: From March 2008 to December 2014, 38 patients were submitted to the revisional procedure. The indication to surgical revision was proctologic in 26 patients and unsatisfactory weight loss in 12. After the revisional procedure, a significant reduction in bowel movements per day was observed, together with a significant reduction in body weight (from preoperative 87.1 ± 21 to 69.2 ± 13.5 kg at post-operative year 1 and 68.1 ± 11.9 kg at year 5; p < 0.001) and a parallel reduction in BMI (from preoperative 33.03 ± 7.6 to 26.8 ± 4.1 at post-operative year 1 and 26.9 ± 2.8 at year 5; p < 0.001). Mean excess BMI percent loss was 49.5 ± 94.6% at post-operative month 3, 76.51 ± 74.9% at year 1 and 76.2 ± 31.3% at year 5. Nutritional and metabolic parameters remained stable. Similar results were observed, analysing separately both groups of patients. CONCLUSIONS: Our preliminary data suggest that the proposed procedure could represent a safe and effective revisional tool to treat invalidating proctologic sequelae after SBPD, or when weight loss may be deemed unsatisfactory.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Clinical and Metabolic Effects of Biliopancreatic Diversion Persist After Reduction of the Gastric Pouch and Elongation of the Common Alimentary Tract. Preliminary Report in a Series of Patients with a 10-Year Follow-Up.

BACKGROUND: Biliopancreatic diversion (BPD) is a bariatric technique burdened, in some instances, by clinical evidence of malabsorption and malnutrition, and by intractable diarrhea. OBJECTIVE: The objective of this study was to assess metabolic and nutritional effects on patients undergoing BPD and BPD plus revisional surgery because of side effects. METHODS: Thirty-five consecutive BPD patients underwent revisional surgery (elongation of the common limb from 50 to 200 cm and reduction of the gastric pouch from 500 to 40 ml) after a median 48-month period [48.3 ± 9.17 months (mean ± SD)] and were observed for a total period of 116.2 ± 6.21 months; 88 patients only undergoing BPD (controls) were observed for 120 months. RESULTS: Revisional surgery significantly improved side effects of BPD, with resolution of clinical symptoms in most instances. After revisional surgery, patients had a further decrease of body weight. The effect on disappearance of diabetes mellitus (DM) was remarkable, with no difference between revisional surgery and BPD. Triglycerides and transaminases decreased in a similar way, while cholesterol levels differed significantly. Estimated glomerular filtration rate improved. Nutritional parameters were similarly affected. CONCLUSION: This study suggests that it is possible to maintain the clinical and metabolic effects of BPD after a revisional procedure that leads to lesser malabsorption and to a greater restriction of the stomach. In particular, the positive effects on DM still persist after revisional surgery. This approach should be kept in mind in the presence of significant side effects due, inter alia, to excessive malabsorption.

Abnormal calcium, 25(OH)vitamin D, and parathyroid hormone after biliopancreatic diversion; correction through elongation of the common tract and reduction of the gastric pouch.

BACKGROUND: Biliopancreatic diversion (BPD) is a surgical technique burdened, in some instances, by clinical evidence of malabsorption and intractable diarrhoea. OBJECTIVES: To compare calcium metabolism together with weight in patients undergoing BPD versus BPD followed by revisional surgery because of side effects of BPD or ineffectiveness of BPD. SETTING: University hospital. METHODS: Twenty-seven patients underwent BPD. After a median period of 48 months, they underwent revisional surgery (elongation of the common limb from 50 to 200 cm and reduction of the gastric pouch from 500 to 40 mL) and were observed for a total period of 120 months; 40 patients only underwent BPD (controls) and were observed for an identical period. RESULTS: At baseline, 24 patients (8 revisional surgery and 16 controls) had increased parathyroid hormone (PTH) levels, and only 3 patients had normal 25(OH)vitamin D levels; calcium declined, even within normal limits, and PTH increased in the revisional surgery group. After revisional surgery, patients experienced a further decrease of weight, together with a reduction of PTH levels, an increase of 25(OH)vitamin D levels, and an increase of calcium levels. Weight loss was inverserly associated with an increase of 25(OH)vitamin D and directly associated with change of PTH. CONCLUSION: This study suggests that it is possible to control effects of BPD on calcium metabolism through a revisional procedure leading to lesser malabsorption and to greater restriction of the gastric pouch. It should be considered in the presence of significant side effects due to excessive malabsorption.