Impact oflaparoscopic sleeve gastrectomy on obesity-associated co-morbidities:A two-year follow-up prospective study

Impact  oflaparoscopic sleeve gastrectomy on obesity-associated co-morbidities:A two-year follow-up prospective study

Nabeel Shdeed,a MD; Mohamed A Mansour,a MD; Ahmed Zeidan,a MD; Hussein  G El-Gohary,a MD; Ashraf  M Abd elkader,a MD;

Ayman M Elbdawy,b MD

a) Departments of General Surgery, Benha University, Benha, Egypt.

b) Departments of  Internal Medicine, Benha University, Benha, Egypt.

Abstract

Objectives: To determine the effects imposed by laparoscopic sleeve gastrectomy (LSG) on obesity-associated  co-morbidities.

Patients & methods: The study included 40 patients; 13 morbid obese and 27 obese patients. All patients  were evaluated  preoperatively for existence  and severity  of co-morbidities and determination of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). All patients underwent LSG; operative time, hospital  stay, and intraoperative and postoperative (PO) complications were registered. Postoperative monitoring included evaluation of the percentage of excess weight loss (roEWL)and the percentage of excess body mass index loss (roEBMIL) at 3, 6, 12 and 24 months after surgery; the frequency of associated co-morbidities and HOMA­ IR index was evaluated at 6, 12 and 24 months after surgery.

Results: Mean operative time was 157.8±17 minutes and mean duration of hospital stay was

5.5±0.9 days. No conversion to open surgery.  All patients  showed  progressive weight  loss throughout the follow-up period with progressively increasing roEWL and roEBMIL. BMI strata showed significant progressive change throughout follow-up period; 27 women were overweight and only 13 women were obese. All obesity-associated co-morbidities showed  progressive improvement  or resolution. At end of follow-up,  7 patients still had co-morbidities, 9 patients had improved co-morbidities and 24 patients had resolved co-morbidities with an improvement and resolution rates of22.5% and 60%, respectively and only 11 co-morbidities were recorded at end of follow-up in various combinations in the 7 non-responders. Preoperatively, all patients were insulin resistant; however, at the end of follow-up period HOMA-IR index of all patients was within the non-resistant range.

Conclusion:  Bariatric surgery effectively  improves  obesity-associated co-morbidities  and

could be considered  as non-pharmacological therapeutic  modality for these co-morbidities. Laparoscopic gastric sleeve is a safe and effective appropriate surgical procedure for morbidly obese patients with associated co-morbidities.

Key words: Laparoscopic sleeve gastrectomy, obesity, co-morbidities, insulin resistance.

Introduction:

Obesity behaves  like  an epidemic with escalating progress up to a fact that the number of overweight and obese people in the world overtook  the number of malnourished},2 As the obesity epidemic increases, health problems associated with obesity became more frequently than ever before; in2007, 41% of women were classified as obese, with a BMI of30 or higher.

A wide spectrum of health problems has been associated with obesity, including cardiovascular disease,  diabetes,  metabolic syndrome and osteoarthritis.3

Sleeve gastrectomy (SG) is a relatively new bariatric procedure involving resection of most of the stomach along the greater curvature to leave only a narrow tube ("sleeve")  between the gastresophageal junction and pylorus. The

remainder of the gastrointestinal tract is not altered. The procedure is typically performed laparoscopically.4,5

Systematic reviews ofbariatric procedures found that SG is comparable to Roux-en-Y gastric bypass (RYGP) with respect to weight loss and improvement in the components  of the  metabolic syndrome. Compared with RYGP, SG has several advantages including the relative  simplicity  resulting  in a shorter duration of surgery and fewer complications. The pylorus is preserved, so patients are less likely  to experience dumping  syndrome. In SG, the small  bowel and mesentery are not altered; as such, there are fewer nutritional deficiencies, there is no added risk of internal hernia, and the entire upper gastrointestinal tract  remains  accessible for endoscopy. A further  advantage of SG is that there  is no permanent  large foreign body installed  as in adjustable gastric  banding  (AGB),  another popular bariatric procedure.6,7

In addition to the usual risks associated with surgery in general and in obese patients in particular,  there are disadvantages and risks associated with  SG compared with  other bariatric techniques. Unlike AGB,  SG  is irreversible, and there is a risk of gastric stenosis requiring treatment  with dilators. The sleeve may  become permanently dilated with overeating. Since the lumen cannot be easily adjusted as in AGB, a second malabsorptive procedure such  as RYGP  may  have  to be performed to promote further weight loss.8,9

The current study aimed to determine  the effects imposed by  laparoscopic sleeve gastrectomy on  obesity-associated co­ morbidities

Patients and methods:

The  present study was   conducted at Departments of General Surgery and Internal Medicine, Benha  University Hospital  since May 2008 till May 2010 to allow a minimum of 2-years follow-up  period for the last case operated on.  After  obtaining written  fully informed patients' consents, the study included

40 morbid obese patients. Obesity grades were defined after the WHO expert consultationlO as BMI <24.9  as average, 25-<30  kg!m2 as overweight, BMI  30-35 kg!m2 as obese and

BMI 35 kg!m2 as morbid obese.Only patients with BMI >30-35 kg!m2 were enrolled in the study. BMI  was  calculated as  weight (kg)lheight (m2).11

All patients were evaluated preoperatively for existence  and severity  of co-morbidities and fasting preoperative blood samples were obtained for estimation of fasting blood glucose and  serum insulin for  calculation of Homeostasis Model  Assessment of Insulin Resistance (HOMA-IR)12  according to the formula  HOMA-IR=  I x G/22.5, where  I is fasting plasma insulin level (JJ.IU/ml) and G is fasting blood glucose in mg/dl, considering an abnormal HOMA-index >3.8.13

Preoperative assessment and preparation:

Individualized  perioperative management was required  based on preoperative history and physical  examination. Diabetic  patients were maintained on subcutaneous injection of regular insulin every 6 hours with dose adjusted according to regular  urine  examination for glucose so as to maintain FBG level  <160 mg/dl, with no ketonuria. Hypertensive patients were maintained on Ca-channel blockers and B-adrenergic agonists so  as  to  maintain S 130, DAP  90 mmHg. Patients receiving treatment for chronic obstructive  pulmonary diseases (COPD) were maintained on bronchodilators and B-adrenergic agonists. All patients with medical diseases were continued postoperatively on the same lines of treatment applied preoperatively.

Operative procedure:

With the patient intubated in supine position, and the surgeon standing between patients legs, preumoperitoneum was  established to  15 mmHg through optical12-mm optiview trocar positioned one and halfhandbreadth below the Xiphoid process, the patient was then placed in reverse Trendelenburg position; lowering the abdominal viscera and freeing the operative field in the  upper abdomen. Then, one 5-mm trocar was placed epigastric subxiphoid position for the insertion of the liver retractor; two working 12-mm trocars were placed on the right and   left   middle clavicular lines, respectively and one 5-mm trocar was placed on the left anterior  axillary line for stomach retraction. Initial decompression of the stomach

with nasogastric tube was performed. After the identification of the gastric antrum at about the distal 7 em from the pylorus on the greater curvature, the greater omentum was dissected from the greater curvature of the stomach with dividing the gastrocolic and  gastrosplenic ligaments up to the esophagogastric junction, Figure(l). The posterior  stomach  wall was visualized and fme adhesions to the pancreas were divided and the lesser sac totally freed. The left side of the  junction was cleared off fat to avoid later compromise of the stapling during creation of the sleeve and left crus was completely exposed, Figure(2). The cutting stapler (60 em long, 4.1-mm staple-height, and green cartridge) Intestinal-Anastomosis (GIA) stapler was introduced through a right trocar towards the left shoulder, and was placed at the point of the initial dissection on the greater curvature, creating  a vertical  on the gastric wall, Figure(3).  Then  a 36-Fr  bougie  was

Figure (1)

Figure (3)

inserted  down to the pylorus and sequential firings of the Endo GIA with 60 mm- 3.5 mm linear staplers were applied over it Figure(4), up to the esophagogastric junction  leaving about 1 em of fat pad along the lesser curvature (3 em width) to assure adequate blood supply on the lesser curvature for the sleeve.The vagus nerves anteriorly and posteriorly were preserved for normal gastric emptying. Reinforcement of the staple line was commenced in all cases by interrupted monofilament absorbable sutures to avoid the risk of postoperative bleeding and leakage, Figure(S).  The  resected greater curvature including most  of  fundus was extracted  via epigastric  or right paramedian trocar-site after being  dilated  to two-fmger diameter. No  drains were  needed and  a nasogastric  tube was left in place. Operative time, hospital stay, intraoperative and postoperative complications were registered.

Figure (2)

Figure (4)

Figure (5)

Postoperative care:

Patients  were maintained in semi-setting position throughout the postoperative period with keeping  an eye on pulmonary  function and continuous capillary hemoglobin oxygen saturation (Sp02) monitoring. The nasogastric tube was removed on the 1st postoperative day, after a normal upper GI  series with gastrographin, and  after assurance of anastomotic line competence  oral soft fluid was allowed  and patients  felt able to return home were  discharged staring  from  the 2nd postoperative day with instructions to follow a liquid diet for four weeks.

Postoperative monitoring:

1. Body weight  and body mass  index were evaluated at 3, 6, 12 and 24 months after surgery and the percentage of excess weight loss (%EWL) and the percentage of excess BMI loss (%EBMIL) were calculated as follows:%EWL = [(Preoperative -Follow­ up weight)/ Preoperative weight]  x 100

%EBMIL = 100- [(Follow-up BMI- 25 I

Preoperative BMI-25) x 100].

2. Associated  co-morbidities  were evaluated at  6,  12  and  24  months  after  surgery.

3.HOMA-IR index was evaluated at 6, 12 and

24 months after surgery.

Results:

The study included 40 patients;  14 males and 26 females with mean age 29.5±2.2; range:

26-34 years. Thirteen patients were morbid obese with mean BMI of41.5±1; range: 40.1-

43.1 kg/m2, while the other 27 patients were

obese with mean BMI of38.4±1.1; range:36.5-

39.7  kgfm2. All patients were  grade III according to the  American Society of Anesthesiologists grading (ASA grade III), as all of them were at least obese and had at least one co-morbidity  or multiple co-morbidities in varied combinations. Twenty-three patients were  type-2 diabetics, 13 patients were dyslipidemic, 21 patients were hypertensive,

26 patients had obstructive sleep apnea syndrome (OSAS), 17 patients had depression/anxiety manifestations and  27 patients had knee or hip joint pain, Table(l).

All patients passed smoothly without intraoperative complications or conversion to open  procedure. Mean operative time  was

157.8±17; range: 130-180 minutes and mean duration of hospital stay was 5.5±0.9; range:

4-7 days. Six patients stayed in hospital for 7 days, 11 patients for 6 days, 18 patients for 5 days and 5 patients returned home on the 4th PO day. All patients were instructed to continue on their medical therapy for strict control of their co-morbidities according to the regimen applied  for preoperative preparation. Three patients were re-admitted; two diabetic patients developed wound infection and were admitted for control of their diabetes and wound infection responded to conservative therapy, while the

3rd patient had a severe asthmatic attack that was managed and patient returned home within hours. Five patients developed esophagitis due to gastro-esophageal  reflux disease (GERD), all responded  well  to conservative medical therapy. Throughout the follow-up period no mortalities  were  recorded  Table(2).

All patients showed progressive weight loss

throughout the  follow-up period with progressively increasing %EWL and o/oEBMIL, Figure(6). BMI strata showed significant progressive change  throughout follow-up period; 27 women were overweight and only

13   women  were  obese,  Figure(7).

All obesity-associated co-morbidities showed progressive improvement or resolution. At end of follow-up,  7 patients still had co­ morbidities, 9 patients had  improved co­ morbidities and 24 patients had resolved co­ morbidities with an improvement and resolution rates of 22.5% and 60%, respectively and only

11 co-morbidities were recorded at end of follow-up in various  combinations in the 7 non-responders, Table(4).

Preoperatively, all patients were  insulin resistant, irrespective ofbeing diabetic or not with significantly higher HOMA-IR index of diabetics compared to non-diabetics. However, at the end of follow-up period HOMA-IR index of all patients was within the non-resistant range, Table(S).

Table (1): Patients' enrollment data.

Data are presented as mean±SD & numbers; ranges & percentages are in parenthesis.

Table (2): Operative and postoperative data.

Data are presented as mean±SD & numbers; ranges & percentages are in parenthesis. PO: postoperative.

GERD: gastro-esophageal  reflux disease.

Data are presented as mean±SD.

Table (4): Frequency of co-morbidities  recorded throughout foUow-up period.

Data are presented as numbers.

Table (5): Insulin resistance data.

Data are presented as mean±SD.

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Figure (7):Plltiema' distribu Wn tla)()rd/llg to BMI strtittl r(!C()rded throughout

follow-upperWd.

Dlsnnlon:

Thecuuentstudy aimed to evaluate gastric

sleevesmpry asamodality ofba:riatric lllllgS)'

on obesity-assO<liated c:o-morbidities; all enrolled pa1iiZ1IJ had co-morbifor a to1al. numberofco-DIOI:bidities of 127oo-motbiditi.es invaried distribution among studied pati«mts. At 24-month follow-up period 116 c:o­ mmbidilielJei1ber11:10lvedtotally orimproved with a  target  succen rate  of  91.3%.

Interestingly, di.abe!es mellitus completely disappeared as co-morbidity.

These data are inline with that ll!pOited in li; Hinojosa et aJ.l-' epo1ted that weigbt loesassociatedwitb.laparoscopiegasW:bypass substantially  improves and/or  resolves hypertension in the majority of patients and improvement occurs as early as 1 month postoperatively and is more frequently in patients with a shoner preoperative duration

of disease. Rao et al.15 found that weight loss brought  about a significant improvement in apnea hypoapnea index and continuous positive airway pressure requirements and laparoscopically placed adjustable gastric band placement should  be considered a broadly effective therapy for  sleep  apnoea in  the severely obese patient.

Shah et al.16 studied 15 patients with BMI

28.9 kglm2 who underwent Roux-en-Y gastric bypass and reported that all antidiabetic medications were discontinued by 1 month after surgery in 800/o of patients and at 3 months and thereafter, 100% were euglycemic and no longer required diabetes medication, and their waist circumference, presence of dyslipidemia, and  hypertension improved significantly. Pappachan et al.l7reportedthat bariatric surgery has emerged as an important and very effective treatment option for  obese individuals especially  in those with co-morbidities like hypertension and diabetes. Gagne  et al,l8 reported that after bariatric surgery diabetes had improved or went into remission in 90%, hypertension had improved or resolved in 62% and obstructive sleep apnea had improved or resolved in 96%. Moreover, Benaiges et al.19 reported that  at 12 months, the overall cardiovascular risk decreased  from 6.6% to

3.4% after both LGS and laparoscopic Roux­ en-Y  gastric bypass without a difference between both procedures.

One  of the interesting outcomes of  the current study is the control imposed by excess weight loss on insulin resistance as judged by HOMA-IR index which showed significant improvement compared to preoperative index. Improvement or resolution of obesity­ associated co-morbidities could be attributed to the significant improvement of IR which underlay pathogenesis of these co-morbidities as documented previously; Cusi  et al,20 supposed that IR is characterized by selective impairment  in phosphatidylinositol 3-kinase (PI 3-kinase)-dependent signaling  pathways regulating metabolic actions of insulin in skeletal muscle with intact mitogen-activated protein kinase (MAPK) signaling pathways. Inaddition, insulin resistance is accompanied by compensatory hyperinsulinemia that serves to  overcome impairment in  PI  3-kinase

signaling to maintain  euglycemia. However, this hyperinsulinemia is predicted to overdrive unaffected MAPK signaling that may promote pathological actions of insulin, including increased expression of vascular adhesion molecules, proliferation of vascular  smooth muscle, increased expression of proin:flammatory cytokines and activation of cation pumps. These factors may shift the balance between vasodilator and vasoconstrictor actions of insulin and result in predisposition to hypertension in insulin­ resistant states.21,22

As regards gastric sleeve as a procedure of bariatric surgeries; all  patients showed a significant progressive %EWL and %EBMIL reaching a maximum at  end  of follow-up compared to at 3-month PO; these  data indicated the applicability of laparoscopic sleeve gastrectomy as a primary and definitive line for management of obesity  and morbid obesity and go in  hand with Givon-Madhala et aJ.,23 and Kasalicky  et aJ.,24 who reported the %EBMIL of 49% and 21% after 4 and 9- month follow-up, respectively. Also, Gagner et aJ.,25 performed  LSG for 63 super-super­ obese patients with average preoperative BMI of68 kglm2 and by 6 months postoperatively, the average BMI had decreased to 58 kglm2 and  to 50  kgfm2 one-year without further surgery. Moreover, Sanchez-Santos et aJ.,26 reported a mean %EBMIL at 3 months of38.8,

55.6 at 6 months, 68.1 at 12 months, and 72.4

at 24  months. Gagner et  al.,5 through  the Second International Consensus  Summit for Sleeve Gastrectomy documented that LSG was intended as the sole operation for an average

%EBMIL of about 60% through 4 years follow­

up and concluded that LSG for morbid obesity is very  promising as a primary operation.

The reported outcome  of LSG  could  be attributed to the fact that LSG is putatively a purely restrictive  operation  that reduces the size  of the gastric  reservoir to  60-100  ml, permitting  the intake of only small amounts of food and imparting a feeling of satiety earlier during a meal. Moreover, it has been suggested that attenuation of endogenous ghrelin levels may also contribute to the success  of LSG; Ghrelin, which  is thought to be  a hunger­ regulating peptide hormone, is mainly produced

in the fundus of the stomach and by resecting the fundus  in LSG, the majority of ghrelin producing  cells are removed, thus reducing plasma ghrelin levels and  subsequently hunger.27-30

It could be concluded that bariatric surgery effectively improves obesity-associated co­ morbidities  and could be considered  as non­ pharmacological therapeutic modality for these co-morbidities.Laparoscopic gastric sleeve is a  safe  and  effective appropriate surgical procedure  for morbidly  obese patients  with associated co-morbidities.

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