Laparoscopic

          Laparoscopic   Management   OF   Large   Hiatus   Hernia

INTRODUCTION

   

      

   The Management of large hiatal hernias is difficult and their operative repair can be technically challenging . The concept of a large  hiatal  hernia, however, has not been clearly defined. They have been classified by various  authors according to whether the hiatal defect  is larger or  smaller  than 5 cm and or / or their  contents. Aly et al considered hiatal hernias to be large when more than 50 percent  of the stomach has migrated into the chest.  Andujar  defined  it as the presence  of more than one- third of the stomach in the thoracic cavity. Carlson et al in his study has  defined  hiatal  hernias to be large if the  hiatal defect is larger than 8 cm which was later  modified to 5-6 cm. We consider paraesophageal hernias to be large  when more than half of the stomach has migrated into the chest or if the hiatal defect is larger than 5 cm in size.

    

    Hiatal hernias are classified into type I to IV depending on the position of the gastroesophageal junction in relation to the diaphragmatic  hiatus. According to the conventional classification, type III and type IV can be considered to be large hernias. Type III hernias, which is a mixed sliding and paraesophageal hernia (PEH)  occurs predominantly in the elderly population . The end stage of a hiatus hernia  is an intrathoracic stomach in which the whole stomach  migrates into the chest by rotating 180 degrees along its longitudinal axis with the caedia and the pylorus as fixed points  and includes other organs including colon, omentum, small bowel , liver and spleen (TypeIV).

   

     Surgical correction of large hiatal hernias is indicated because of unsatisfactory outcomes after long- term medical  management and potentially disastrous consequences of gastric incarceration or volvulus  in large paraesophageal hernias. Fundamental steps involved in large hiatal hernia repair include a tension free reduction of the esophagus  and the stomach into the abdomen with complete excision of the hernial sac, reapproximation  of the hiatus, and subdiaphragmatic  fixation of the stomach, with many authors advocating the additional of an antireflux procedure.

     Recurrence rates after laparoscopic surgery is a controversial and unresolved  issue. A few early studies have shown alarmingly  high recurrence rates. Some possible patient related and procedure  related mechanisms are  in appropriate postoperative activity  of the patient immediately after surgery, inadequate excision of the sac, inadequate mobilization of the esophagus, inadequate crural closure secondary to widely spaced crura sutured  under  tension , or a postoperative rupture of crurorraphy due to continuous excursion of the diaphragm.

   

     After complete reduction of all the hernial contents, the necessity of complete excision  of the  hernial  sac cannot be understated. IN  earlier series recurrence rates of up to 20 percent have been  reported after inadequate excision  of the hernial  sac . Although  sac removal is tedious and difficult,it is one of the most  crucial  steps of large paraesophageal  hernia repair. If  circumferential  reduction of the sac  is not done and a portion  of the  sac of new  hernia formation has been  practically  left behind. Fluid collections in the unresected sac leading to postoprative dysphagia have also been reported in literature.

   

     A number  of methods have been adopted to reduce the risk of postoperative recurrences and include the use of Teflon pledgets to prevent crural sutures from cutting through, complete detachment of the sac from the hiatus and mediastinum, complete excision of the sac, adequate mobilization of the esophagus and use of mesh cruroplasty in patients with a large hiatus hernia to achieve a tension free hiatal.

SURGICAL PRINCIPLES
    

     

    Although the need for surgical repair is undebated, controversies exist concerning the best surgical  approach  whether open or laparoscopic, the presence of short esophagus and the need for an esophageal lengthening procedure, crurorraphy or a tension free mesh repair, subdiaphragmatic  fixation of the stomach , the need for an antireflux procedure, whether total or partial fundoplication and the indication for prosthetic  reinforcement of the hiatus.

GALLSTONES

                                           GALLSTONES

                 

      Biliary tract  disease is the second  most common  non- obstetric  surgical problem, though it affects only 1 in 1600  to 10000 pregnancies. Cholelithiasis has been documented in 10  percent  of pregnancies and  cholecystitis reportedly affects  0.1 percent  of pregnant patients.

        Pregnancy related  physiological  changes : a. Progesterone causes smooth  muscle relaxation  and  a decrease  in gallbladder tone.  Weakened  contractions and  decreased  emptying  lead to increased  gallbladder  volume  during  fasting  and after eating. In  turn, biliary  stasis  contributes  to cholesterol  crystal sequestration ,  theoretically leading to the  formation  of sludge and stones. b. Elevated  estrogen levels during  pregnancy may further  increase the lithogenicity  of bile. c. Lower  gallbladder  ejection  fractions  and increasing  parity seem  to increase the risk of  sludge formation. A high pre-pregnancy body mass  index  also  may increase the  risk  of sludge  formation. Despite these  physiologic changes, it is unclear if  pregnancy increases  the incidence of gallstones  and  cholecystitis . In  a German  population  study looking  at 1111 females, current pregnancy and the number of prior pregnancies were not associated with an increased  risk.

       The clinical presentation of acute  cholecystitis is similar  to the non- pregnant patient. The pregnant - patient who has right upper  quadrant  tenderness  should undergo ultrasound  evaluation  first because it is  noninvasive and quickly obtained.  MR cholangiography can be suspected  but not demonstrated on  ultrasound.  Symptomatic  cholelithiasis often is managed initially with  a conservative approach,  delaying elective cholecystectomy until after delivery. If conservative  management fails, or if repeated hospitalizations are required, especially  in the same  trimester, cholecystectomy is indicated. Recent studies have  shown, earlier surgical intervention  for biliary tract disease in pregnancy is safe with reduced hospital stay, reduced use of  medications, lower rates  life- threatening complications and lower preterm deliveries. The  laparoscopic cholecystectomy  has been performed safely in all trimesters. The use of an  open  technique for entry, insufflations to 12 mm Hg, and  maintaining a left lateral decubitus  position minimize risk to the fetus and  help maintain adequate placental blood flow during  surgery.

        Patients presenting with acute cholecystitis and symptomatic choledocholithiasis  during pregnancy  should be considered  in a higher  risk  category. If  complications such  as cholangitis or gallstone  pancreatitis develop, maternal mortality  approaches 15 percent, and fetal loss occurs in 60 percent of cases . 

        Surgical approaches  include open cholecystectomy with choledochotomy  or laparoscopic  cholecystectomy with ERCP (endoscopic retrograde cholangiopancreatography ) with sphincterotomy  for  stone extraction or stent placement has been shown  to be  safe during pregnancy.  Although  not routinely recommended, intraoperative  cholangiography   is safe  after fetal organogenesis is complete  and does not increase the risk   of preterm  labor or adverse fetal outcomes.

APPENDIX

                                                      APPENDIX

       

     Appendicitis is the most common non- obstetric surgical complication and the most common gastrointestinal disorder  requiring  surgery during pregnancy. It accounts  for 25 percent of surgeries for non- obstetric  indications in  pregnancy and complicates every  1 in 1500 to 2000 pregnancies. The incidence of perforated  appendicitis in pregnant women is 43 percent compared to 4-9 percent in the non- obstetric  population.  This increased  incidence may be due to delay in diagnosis and reluctance to operate in pregnancy. Maternal and fetal morbidity and  mortality correlate with perforation and  its associated complications. Uncomplicated appendicitis has a 3-5 percent  fetal loss rate with negligible maternal mortality. Appendix perforation, however, is associated with a 20-35 percent fetal loss rate and 4 percent maternal mortality. Appendix  perforation , however , is associated  with  a 20-35 percent  fetal  loss rate and 4 percent  maternal  mortality. Maternal  mortality rates have  dropped  significantly in the  recent  years with prompt surgical  intervention , newer antibiotics and  surgical  techniques. 

      The preterm contractions  caused  by  uterine irritation from perforation peritonitis result in preterm delivery in 5-14 percent. This incidence is similar between  open  and laparoscopy. In the  first trimester the  appendix remains in its  normal anatomic  position. The appendix  undergoes progressive displacement cephalad  and laterally with advancing pregnancy. After 24 weeks gestation, the  appendix is shifted superiorly  above the right iliac crest , and the tip of the appendix is rotated  medially toward the uterus. By  late pregnancy, the appendix may be closer to the gallbladder than MCBurney's point, occupying the right upper quadrant . This change may alter the location of the pain, making diagnosis difficult. As the  peritoneum is displaced  from the appendix  and cecum by the growing uterus, the increased separation of  the visceral  and parietal peritoneum  decreases  the somatic  sensation of pain and compromises the ability to  localize pain  on examination. The enlarging uterus interfere with the ability  of the omentum and bowel to wall off the inflamed appendix.  Diffuse peritonitis from perforation is  facilitated by this inability of the omentum to isolate the infection. The appendix  returns  to its normal  position by the tenth postpartum day. However, modern clinical experience does not confirm this assertion, with recent studies demonstrating  that the most frequent  location of pain  remains in the right lower quadrant, regardless of trimester. 

               

     Symptoms of appendicitis often  are confused with normal  pregnancy related conditions, particularly in the third trimester. Pain in the right lower quadrant is the most  common and reliable symptom  of appendicitis along with the usual features of appendicitis. Rectal  and pelvic tenderness may not be present when the appendix  is displaced by the uterine enlargement. Leukkocytosis is normal in pregnancy  and so not a good  indicator. Ultrasound Scan is useful  in the first  and second trimester. MRI is safe in pregnancy . CT  Scan should be reserved for cases where Ultrasound and MRI are non- diagnostic. Despite reluctance to operate on a pregnant patient, immediate surgical  intervention is indicated when a  diagnosis of appendicitis is made. The choice of surgical procedure is  based on uterine size and experience  of the  surgeon.  The only indication  of delay  is active labor, and in these  cases the surgery is performed immediate  postpartum.

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      Diagnostic and operative  laparoscopy  is reasonable  before 20 weeks gestation  and is as safe as open surgery. When  performing  laparoscopy  open entry(Hassan)  is preferable to avoid inadvertent veress or trocar  entry into uterus. Trocar placement  needs to be changed according  to the  size of the uterus. Beyond the late second trimester, laparoscopy  becomes more technically challenging . Appendicitis is confirmed in 36-50  percent of cases. Accuracy of diagnosis  in the  first trimester is greater.  A higher false positive rate is acceptable  in pregnant women, because  any delay in diagnosis may compromise maternal and fetal  well - being .

THE DIABETIC FOOT

                                       

   
    An  important  underlying  cause leading to diabetic foot problem is neuropathy. Sensory  neuropathy  leads  to a loss of  protective  sensation. Foot  trauma  is unrecognised and leads to ulceration. The ulceration is often the portal of entry for bacteria, leading to cellulites and/ or abscess formation. Motor neuropathy can lead to asymmetric  muscle atrophy, foot deformity (equines deformity) and altered  biomechanics. This  leads to areas of high pressure during standing or walking and repeated  trauma  that may go unrecognised  because of sensory deficit. Autonomic neuropathy results in loss of sweating and dry skin that leads to cracks and  fissures and a portal of entry for bacteria. Diabetes is also associated with an increased risk of peripheral arterial disease and it can be a major factor in non- healing of foot ulcerations.
 
     Diabetic patients can have significant foot infection, with much less pain and no pronounced systemic inflammatory response. A high index of suspicion is therefore required to diagnose foot infection in patients with diabetes.
                                                   

     The skin of the foot is a highly specialized organ. The plantar skin consists of a complex array of fascia, fibrous septae and tangential shearing forces that occur during walking. The dorsal skin is bound to the underlying extensor retinaculum.  Infection tracks along fascial  planes and tendon sheaths. The location of a diabetic foot wound will usually lead surgeon to the underlying cause. An  ulcer at the posterior border of the heel is usually the result of chronic pressure from prolonged contact with bedding, friction from rubbing against rough bed sheets and lack of elevation. An ulcer about the plantar foot is almost always due to i) excessive pressure and time between the foot and the contact surface, ii) neuropathy and iii) deformity of the foot ( equines contracture). Understanding  the underlying cause will allow an effective wound care. The single best means of reducing pressure on the sole of the foot  is to employ non- weight bearing of the involved  limb through use of crutches or walker. This  may not always be practical but effort should be made to emphasize compliance. Use of standard off- loading shoes are also recommended.
   
    Pain in a neuropathic  foot is usually related to an underlying infection. After a thorough surgical preparation, in the emergency room, to remove debris and allow proper evaluation, the wound is probed to determine its depth and tissues involved. Osteomyelitis should be considered if the wound is deeper than the dermis layer. Most patients with diabetes who present  with a severe foot infection have chronically poor glycemic  control, chronic anaemia, poor nutrition and deficient clinical care. Therefore, laboratory studies and necessary management is essential  before embarking on active treatment.

                                                             

    An important initial  step in treating limb threatening diabetic foot infection is to perform a timely and adequate surgical  debridement. This entails surgical excision of all nonviable and/ or infected  tissue. The plantar spaces are opened by longitudinal incisions with division  of plantar fascia. When pus is present in flexor tendon sheaths, these are opened and drained. In order to appropriately evaluate the viability of the soft tissues and the underlying structures, surgical  debridement should be performed without the use of a tourniquet. If there is exposed bone or suspicion of osteomyelitis, cultures are obtained of this tissue. Wound is irrigated and meticulous hemostasis achieved. Most diabetic foot infections are treated with an empirically selected antibiotic regimen until cultures and sensitivity are available . In a limb threatening infection or osteomyelitis, intravenous therapy should be initiated and followed if possible by oral agents. The use of topical antibiotics has a limited place as may produce the development of resistant strains of colonized surface bacteria.

    A patient with diabetes may not give the typical history of claudication because of associated  neuropathy or lack of activity. It is therefore  important to evaluate the limb for peripheral arterial disease even  in the absence of symptoms. If pedal pulses are not clearly palpable, further vascular studies are indicated. An ankle- brachial index (ABI) should be obtained.

      There is a close association between peripheral arterial disease and coronary disease making then both a high risk for a traditional open bypass procedure. The endovascular options include percutaneous angioplasty  with or without a stent . These procedures cab be performed under local  anaesthesia and sedation and with a high rate of limb salvage .

      The standard treatment of diabetic foot ulcer includes adequate off- loading of weight, frequent ulcer debridement , wound care, treatment of infection and revascularization of ischemic limb. This standard  care in many controlled trials  has resulted in healing of a number of foot ulcers.  However, newer therapeutic  modalities that can improve healing also need to be explored.

     Despite recent advances in surgical and radiologic vascular techniques, a fair number of patients with critical limb ischemia are not eligible for a revascularization procedure.  This is because of anatomic location of the lesion, the extent of the disease or extensive co-morbidity . No  effective pharmacologic  therapy is available  and amputation is often  the only option left.  The cost of managing a patient after amputation has been estimated to be almost  twice that of a successful limb salvage . Therefore, exploring new strategies for ischemic limbs is of major importance.  Bone marrow derived progenitor cells have been identified as a potential new therapeutic target.

    Normal wound healing is a intricate process involving various  cell types, coordinated processes, and complex signaling  interactions.  In a diabetic wound , many of these  responses to inflammatory mediators, matrix production, angiogenesis, and wound contraction have all been  poor and contribute to delayed  healing of a diabetic wound.

     Cell - based therapy is an attractive approach for the treatment of wounds with multiple impairments. Mesenchymal stromal  cells (MSCs) are the multipotent cells derived from stroma  of bone marrow  and other tissues. The local delievery  of  MSC to a diabetic wound might  correct wound healing impairment both indirectly by reversing local  growth - factor deficiency, and directly by improving wound contraction through  interaction with the extracellular  matrix. The decrease in wound size  might  have the potential to offset diabetic - related wound - healing impairment  significantly.
                                                 

       In a  randomized  controlled  trial in 28 diabetic patients with critical limb ischemia, Huang et al reported improvement in limb ischemia and foot ulcers.  By far the most studies of cell therapy have used intramuscular implantation method or intraarterial  injection. Progenitor cell- based  therapy may have great clinical potential.

TISSUE ENGINEERING

                                               

   Tissue engineering may allow the patients 's own cells to be obtained and seeded onto bio- degradable scaffolds that permit the formation of a particular tissue. These tissues can be employed to repair tissue defects caused by disease of trauma. Furthermore, tissue engineering may allow the ex- vivo engineering of tissue by means of  three- dimensional  bioscaffolds seeded  with mature cell or stem cells and cultivation in bioreactors leading to the formation of whole tissues or organs, e.g, liver, heart, cartilage, e.t.c .
    MSCs are good candidates for tissue engineering protocols . Several  scaffolds are currently available and may be classified as biologically derived polymers isolated from extracellular matrix, plants, seaweeds (e.g. hydroxyapatite, tricalcium phosphate, polyactide and polyglycolide) or a combination of both.
     Mesenchymal  stem cells (MSCs)  are characterized by their capacity  for self- renewal and the production of multiple lineages whereas MSCs exist in many other tissues, e.g. skeletal muscle, fat, spinal membrane.
   Embryonic stem cells offer higher pluripotency but remain problematic in clinical use because of ethical issues. In contrast MSCs harvested from adult organisms are ethically uncomplicated and readily available. However , the harvesting of these cells requires  invasive procedures and adult MSCs have poor quality when compared with embryonic stem cells (Baxter et al, 2004; Roura et al, 2006. )
                                                             

    Stem cells with fetal origins have the potential to offer the ideal balance between quality and ethics. Fetal cells from fetal tissue such as umbilical cord, umbilical cord blood or placenta  may  lie in between (Embryonic  and adult ) with respect  to quality and quantity.
     This is an attractive source for clinical applications and more studies should be carried out.
     Polyglycolic  acid nonwoven mesh tubes coated with copolymer solution were seeded with autologous bone marrow derived mononuclear  cells and a living autologous  vascular graft with growth  potential  developed . This is for advancing the field of congenital heart surgery..The currently available synthetic vascular grafts such as PTF  lack growth potential  and present problems related  to biocompatibility including thrombosis , ectopic  calcification and increased susceptibility to infection.
    Due to lack of growth potential  the surgery  needs to be delayed until the patient recipient has grown to a suitable  size to allow for inflammation  of an adult  size graft.
   Tissue engineered graft in the surgical repair of congenital anomalies is cearly  established.
    Mesenchymal  stem cells are an attractive cell source for regenerative  medicine.
      Bone marrow aspirate is obtained from the iliac crest. Synovium is harvested  from the knee joint. Adipose tissue can  be harvested from perinephric  fat tissue. Muscle was harvested  from anterior  tibial muscles.
     Cells from various sources were studied. Synovium and muscle derived cells had a higher  proliferation potential than bone marrow and adipose derived cells.. The  earlier  types had much more chondrogenic potential.
     Transplanting autologous chondrocytes  cultured in collagen  gel has been reported  for the treatment of full thickness  defects  of cartilage.
     Neovascularisation  is a critical step in tissue engineering applications, since implantation of voluminous  grafts without  sufficient vascularity results in hypoxic cell death  of central  tissues. A three dimensional  spheroidal co culture system consisting of human  umbilical vein  endothelial  cells have been developed to improve angiogenesis in tissue engineering.  Human  umbilical vein endothelial  capillary grown in collagen  gels are able to form luminized  capillary like structures and there is stimulatory effect of fibroblasts on endothelial cell sprouting .

                                                                 

Cell Therapy For Spinal Cord Injury

                                    

  Spinal   cord injury has no curative therapy at present . For a future efficient treatment one has to consider and combine the following approaches :
1. Tissue or cell transplantation ,
2. Providing growth stimulating factors. There is direct  disruption  of nerve tracts with secondary  damage done to oestemia and  hemorrhage. The glial scar forms at the site and is a barrier for future representations of the brain .
    
   Therefore in the acute setting, secondary damage is linked by decompression of the  spinal cord by laminectomy  to limit ischemia, orthopaedic fixation of the  involved  vertebrae  and high dose of steroids.
    
    Currently, the existence of endogenous mechanisms for neural  regeneration is being  accepted. In multiple  animal studies the presence of neural  stem cells in different areas of brain has been . Uchida et al have documented the existence  of adult neural stem cells in the subventricular zones of the brain .
     
                                                    

      During the last decade,

multiple attempts in animal  models of spinal cord injury have been investigated. The approaches have focused  on  I) replacement  of damaged  neural tissue, II) enhancement  of endogenous  neural  regeneration , III) modulation of inflammatory  response  after spinal cord injury .
       
     Mc Donald et al differentiated murine embryonic stem cells into neural progenitor cells and transplanted these  cells into a rat model of spinal cord injury with success. Transplantation of adult neural  stem cells isolated post-mortem out of human brains was associated with extensive remyelination comparable with myelination pattern  of Schwann's cells in the peripheral  nervous system, when transplanted in the demyelinated rat spinal cord.

         Others reported improvement after transplantation of murine neural stem cells embedded in a polymer scaffold  in a hemi section model in rat. Despite all the above success with cell therapy , immunological rejection has to be noted.
     
    To circumvent this problem of rejection MSCs residing in bone marrow have received much attention. These can be cultured easily out of bone marrow and in vitro have shown trans- differentiation into neural cells .
    
    After transplantation into brain and spinal cord their differentiation into cells with neuronal and astrocyte characteristics was reported.
      
     Olfactory ensheathing cells have been extracted in humans and their transplantation has improved motor and sensory recover after spinal cord injury.
      
     These results are encouraging and the autologous nature has the relative ease of obtaining these cells and is a good therapeutic  treatment  for spinal injury.

Diabetic Retinopathy

Diabetic  Retinopathy

Discussion
   Diabetic retinopathy  is the most  common cause  of newly diagnosed legal blindness amongst  the working  population  in the  industrialized  world today. . Although majority  of diabetic patients have retinopathy of varying severity, approximately 25% of the  diabetic patients have sight - threatening diabetic  retinopathy which  leads  to legal  blindness  (best corrected visual acuity of 20/200 or worse ).  Blindness  due to retinopathy  is 25 times more common in the diabetic, when  compared to the non diabetic population.
    Approximately 10 % of the  diabetic  population has type  1 (insulin- dependent) diabetes mellitus, which is usually diagnosed before  the age of 30 years. The majority (90%) of diabetic patients, however have type 2 ( non- insulin- dependent )  diabetes mellitus, which is diagnosed after the age of 30 years. Diabetic retinopathy is a highly specific vascular  complication of both type 1 and type 2  diabetes mellitus, and the duration  of diabetes  is a significant risk factor for the development  of retinopathy.
   Macular oedema  represents  a common pathologic  sequel of the  retina associated  with a  broad spectrum  of potential  insults. Diabetic macular oedema (DME) can occur at virtually  any  stage during  diabetic  retinopathy  development , and it represents  the leading  cause of visual  impairment in people with diabetes.  One of the most common  causes of  macular oedema is diabetes mellitus, and it is the cause  of visual loss in the latter.  The duration of macular oedema could be an  important  factor for visual prognosis.

   Molecular  basis  of  diabetic retinopathy . The retinal changes in patients  with diabetes resulted from five fundamental processes:
I)  the  formation of retinal  capillary  micro aneurysms, The development
II) the development  of excessive vascular permeability,
III)  vascular  occlusion ,
IV) the proliferation  of new blood vessels and accompanying  fibrous tissue on  the  surface  of the retina  and  optic disk, and
V )  the  contraction of these  fibro vascular proliferations and the  vitreous.
   
  The  clinic pathological lesions  of diabetic  retinopathy have been  well  classified. Although a  multitude of pathogenic  mechanisms  have  been   proposed, the underlying  dysfunctional   biochemical and molecular  pathways that lead to  initiation and  progression  of DR still remains an enigma. Currently  four  major  biochemical  pathways  have been  hypothesized  to explain  the mechanism  of diabetic  eye diseases all starting initially from  hyperglycaemia  induced  vascular injury. These  mainly  include:

I) enhanced  glucose  flux through  the  polygon pathway,
II)  increased  intracellular  formation of advanced glycation  end- products (AGE),
 III )  activation of protein  Kinase C (PKC) is forms, and
IV)  stimulation of the  hexosamine pathway.
   
   Studies have suggested that  these  mechanisms  seem  to reflect  a hyperglycaemia  induced process initiated by superoxide  overproduction  by  mitochondrial  electron transport  chain. Studies  have shown that poor glycaemia  control and higher levels  of HbA 1 c are among the risk  factors for  the onset of DME.  The  Wisconsin Epidemiologic Study  of  Diabetic Retinopathy  found rates  progression to DME of 26% in patients with diabetes  for 14 Years  and 29 % at  20 years or longer after diagnosis.

 
   
  Diabetic  retinopathy (DR) is a  very  common , potentially preventable, long - term complication of type  1 diabetes and the leading cause of  acquired  loss of vision among working - age adults in  Europe  and North America. Most  vision loss  in diabetes is a  result  of  diabetic macular  oedema, which  results  after  breakdown of the blood retinal barrier. Diabetic  macular  oedema is the  result  of retinal  micro vascular changes that occur  in patients with diabetes.  Thickening  of the basement membrane  and  reduction  in the number  of  pericytes is  believed to lead  to  increased  permeability  and  incompetence of

retinal  vasculature.  This  compromise  of the  blood- retinal  barrier  leads  to the leakage  of  plasma  constituents in  the  surrounding  retina,  resulting  in retinal  oedema.  The  hypoxic  state  achieved  through  this  mechanism can also stimulate the production of vascular endothelial  growth  factor (VEGF).  Macular  oedema affects approximately 29% of patients with diabetes  who have  disease  duration  of 20 years  or longer  and  constitutes the primary  cause  of visual  impairment  in  this  population.  For 30  years  the standard  of  treatment  has been  glycaemia  control  and  photocoagulation.  Despite  this,  some patients  suffer  permanent  visual  loss  even  after  intensive  treatment.  Despite  intensive  study,  current  understanding  of the  pathogenesis  of  diabetic  macular  oedema  remains  incomplete.  Hyperglycaemia  is clearly  the  strongest  known risk  factor for  DR.  Nevertheless,  whereas  intensive  glucose  lowering  was  effective  in  substantially  reducing  the  incidence  and  progression  of  retinopathy  in  the  Diabetes  Control  and  Complication  Trial (DCCT), there  was no  statistically  significant  effect  on the  incidence  of clinically  significant  macular oedema (CSME) during  the trial.  Thus, other  factors are  likely  to  play  at least  a contributory  role  in the  pathogenesis of CSME.

End - Stage Kidney Disease

End - Stage Kidney Disease

     End- stage kidney disease is the final stage of chronic kidney disease (CKD), which is also known as chronic   renal  disease (CRD).  This  final  stage, stage 5 CKD, is also known  as chronic kidney failure (CKF), chronic renal failure (CRF) or end stage renal disease (ESRD). Chronic  kidney  disease is a progressive  loss of kidney function  (renal function ) that  continues over a span of months to years, through  the five stages. The  progressive of the  kidney disease is measured  by the lowering  of the  glomerular  filtration  rate (GFR). This is usually  measured  by the  level  of  creatinine  in the patient's  bloodserum. Patients  with  a GFR of less than  60 mL /min/1.73 m are  considered  to have  chronic  kidney disease, regardless  of whether  kidney damage is present and noticed . At  this  level, the GFR is already lowered  by at least half of the normal adult level of healthy kidney function.
     Chronic renal failure(CRF) requiring dialysis or transplantation is known as end- stage renal disease  (ESRD). In the  United  States, diabetic nephropathy is the most common and hypertension   the second  most common  cause.  Along  with  glomerulonephritis, these  cause  approximately 75% of all  adult cases. Certain  geographic  areas  have  a high incidence  of HIV  nephropathy.  Genetic  kidney disease such  as  polycystic  kidney disease is a common  cause in young  adults.  Patients with end- stage renal disease (ESRD)  are  commonly encountered in the emergency departments (ED) with  problems  related  to the  metabolic  complications  of their  renal disease  or dialysis complications.  Various  problems related to vascular access in patients on hemodialysis  and to  abdominal catheters in patients  using continuous  ambulatory  peritoneal  dialysis(CAPD)  are also common. Patients  who have undergone renal  transplantation  may experience a  variety of transplant- related conditions.
   All  major organ systems  are affected  by renal  failure. Prevalence of symptoms is a function of the  glomerular  filtration  rate (GFR) , which  averages  120 mL / min in a healthy  adult.  As the GFR  falls to  less  than  approximately 20% of normal, symptoms of uremia may begin to occur. They almost are invariably  present  when  the GFR decrease to less than 10% of normal. Measuring  GFR  requires a  timed  urine collection as well as measurement  of serum  creatinine. However, it  can be  accurately  estimated  from   a  patient's age,  weight,  gender, and  serum  creatinine  level.
   Signs and  symptoms of  renal  faiure  are due to overt  metabolic  derangements  resulting from inability of failed kidneys to regular  electrolyte, fluid, and acid- base balance, they are also due to  accumulation  of toxic products of amino acid metabolism in the serum.

INCIDENCE  AND  PREVALENCE

      During  2004, the last year with  complete data availability , 104,364 patients (approximately 0.03% of the  US population )  began renal replacement  therapy, an adjusted  incidence rate of 339 per 1,000,000 . As  of 2005 , more than 485,000 patients were receiving treatment for ESRD in the United States . As a result, patients with ESRD are encountered on a regular  basis in US emergency departments .

International

    The  morbidity and mortality of dialysis  patients is much  higher in the United States  compared  with most other countries.  This  is probably a consequence of selection  bias.  Due to liberal  criteria for receiving  government - funded  dialysis  in the  United States  and  rationing  (both medical and economic )  in most other countries, US patients receiving dialysis  are on the  average  older and sicker than those in  other countries .

Mortality / Morbidity

 Patients in renal failure  are  prone  to all of the  complications  of any underlying condition, such as diabetes and hypertension .  In  addition,  renal failure causes a variety of metabolic  and  physiologic  derangements .
   The most  common  cause of sudden  death in patients with end- stage  renal disease (ESRD) is  hyperkalemia , which is often  encountered  in  patients  after  missed  dialysis  or dietary  indiscretion .  Serum  potassium  also  rises  when the serum is acidemic, even though  total  body  potassium  is unchanged .  Hyperkalemia  is usually asymptomatic and should  be  treated  empirically  when  suspected  and  when  arrhythmia  or cardiovascular  compromise  is present .
- Iatrogenic  complications  related  to  fluid  administration  (fluid  overload)  or  medications  are  frequently  encountered  in  patients  in  renal  failure .
-  Cardiovascular  mortality  is 10-20 times  higher in dialysis  patients than in the  normal population .
-  Anemia  results  in  fatigue  reduced  exercise  capacity,  decreased  cognition, and  impaired  immunity .
-  Renal  transplant  patients  are  prone  to  infection ,  especially  in  the  immediate  post- transplant  period .

Race

 Etiology  of end- stage  renal  disease  (ESRD)  differs among  racial  groups  primarily  because  of the prevalence  of  predisposing conditions, such as  diabetes and  hypertension. In  populations with  problematic  access  and  utilization of  primary  medical  care  for treatment  of   predisposing  conditions,  ESRD  often  is  encountered  in  relatively  young  patients.  Diseases  such  as  diabetes and hypertension  are much less likely  to lead  to renal  failure  when  appropriately  treated . The cost  of primary  care  for  these  conditions is  far  lower  than for  dialysis or  transplantation, yet  primary  care  remains  poorly  funded,  while  ESRD  treatment  is  reimbursed  completely  by the  government .
  In the  United States , racial  and  ethnic  discrepancies in  ESRD  exist, with 2006 rates in  the  African  American  and  Native  American  populations 3.6 and  1.8 times greater, respectively,  than  the rate among  whites, and  the  rate  in  the Hispanic  population 1.5 times  higher than  of  non- Hispanics

Sex

 Presentation  and  treatment  of  chronic  renal  failure (CRF) and end- stage renal disease (ESRD)  do not differ  significantly  between  men  and  women . Differences  in causes  of renal  failure  are  related  to the  types of  underlying  conditions  prevalent  in men  and  women.

Age

While  the  etiology  of  CRF  differs  among age  groups, the presentations and  nature of  complications  are  similar.  Young  children  with  ESRD  often  are  treated  with  transplantation  rather  than  dialysis  because  of a  relatively greater long- term  benefit  compared  to that  of adults, and  due  to  difficulties  related  to  vascular  access  for  dialysis .

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Developments in live donor renal transplantation

Developments  in live  donor renal transplantation

     Live Kidney donation is assuming a prominent role in renal transplant  programmes because of the persistent increase in patients requiring  definitive treatment  for end- stage renal failure . While cadaveric transplant rates remain more or less static, live donor transplantation  has increased 3-fold in US over the past  decade,  where  it now accounts for 43% of renal  transplant  activity. Figures of United Kingdom  Transplant  indicate 24% of all  renal transplants were from live donors for the  year  2003-2004. Superior recipient  post -transplant outcome  compared  to cadaveric Kidneys, the potential for transplantation  before  dialysis , and the ability to plan the procedure ( allowing optimisation of recipient condition ) justify this growth  in live donation. New techniques and novel approaches have been developed to facilitate live donation  and  increase  transplant activity.  This chapter presents some of the important recent developments and controversies in live  donor renal

PRE- OPERATIVE IMAGING OF LIVE RENAL DONORS

   PRE- operative imaging of live donors is mandatory for a number of reasons it confirms the presence of two functioning Kidneys, identifies their position, indicates adsence of pathology that would preclude donation, and provides  anatomical information  necessary for planning  the procedure.  The ideal form of imaging is minimally invasive and provides accurate morphological information  on the  renal parenchyma , collecting system and vascular anatomy. Traditionally , imaging has been performed using  angiography, but there are inherent risks with this invasive  procedure . Venous imaging  is limited  with arterial contrast injection, and  separate excretion  urographic studies are  necessary to visualise the collecting  system. These  disadvantages have been the driving force  behind the introduction of computed tomographic  angiography(CTA) for anatomical assessment of living renal donors. CTA is non-invasive and cheaper than other imaging techniques. Pre- operative anatomical  information is, of course, necessary for open donor nephrectomy, but it assumes paramount importance in the laparoscopic procedure because of reduced  exposure, and  particular difficulties in the identification of complex  renal vein  tributaries. Thus, the location , size and number of renal veins and  tributaries need  to be described  accutately pre- operatively. Spiral CTA  imaging compares favourably with conventional angiography  in the prediction   of gross renal arterial  and venous anatomy and  is a powerful tool for identification of renal vein tributary anatomy.

   Prior to imaging , all potential donors are assessed  by physical examination , undergo blood group and HLA  matching with the intended recipient, complement- dependent  cytotoxicity cross - matching , and isotope GFR measurement . At the Leicester unit, CTA is performed  on a spiral GE Prospeed  SX scanner. Arterial and venous anatomy is evaluated using a dual phase protocol with venous injection of iodinated  contrast media (Iopamidol).Arterial phase imaging is performed from the level  of the  coeliac axis orgin to include the lower renal  pole.  Venous phase  imaging (60 s after contrast  injection ) includes the  cephalo - caudal  extent of the left renal  vein and  the left  renal  sinus.

DEVELOPMENT OF MINIMAL  ACCESS DONAR NEPHRECTOMY

     The live donor nephrectomy operation has traditionally been performed through an open incision ,necessitating  a prolonged period of recovery. This, and the cosmetic implications of a large  flank wound may be discouragements to potential donors.
      To reduce such disincentives , there has been a move towards minimally invasive donor nephrectomy, first performed  as a classical  transperitoneal laparoscopic procedure (LapDN) by Louis Kavoussi and Lloyd Ratner in 1995. Retrospective  reports  suggest LapDN is associated with decreased severity and duration of postoperative pain , shorter  in- patient stay, quicker return to work  and normal  activities, and  improved cosmetic result  when compared  to open donor nephrectomy. Furthermore, the overall  societal cost of LapDN is lower and recipient  quality of life scores are higher.
   Despite the current lack  of published statistically  powered randomised clinical trials, retrospective data suggest that minimal access donor nephrectomy not only offers  postoperative advantages to the donor but also increases the number of transplants performed by reducing donor disincentives: estimates range  from a 25% to 100% increase in transplant activity.  In the US, 31% of live kidney donor procedures  are performed  laparoscopically, and 65%  of centres offer the procedure. Despite  encouraging  UK figures indicating  year- on -year increase in  live donor activity, few centres have adopted minimally invasive techniques. With  accumulating evidence that high quality grafts can be procured from  laparoscopically- procured kidneys, the main hurdle for expansion of  laparoscopic donor nephrectomy is lack of operative experience of the technique  amongst UK  transplant surgeons. Three approaches  have been described  and  advocated, comprising  transperitoneal, extraperitoneal, and  hand - assisted live donor nephrectomy. The  hand- assisted operation is said to be easier  to learn than transperitoneal laparoscopic donor nephrectomy, and can be safely  and efficiently performed by surgeons with less laparoscopic experience.  The  retroperitoneal approach  avoids breaching the peritoneum, and may also have a particular application in right donor nephrectomy.

                                               

Insurance

Insurance

Insurance is that the even handed transfer of the chance of a loss, from one entity to a different in exchange for payment. it's a kind of risk management primarily accustomed hedge against the chance of a contingent, unsure loss. An insurer, or insurance carrier, is merchandising the insurance; the insured, or customer, is that the person or entity shopping for the insurance. quantity|the quantity|the number} of cash to be charged for an explicit amount of amount is termed the premium. Risk management, the follow of evaluative and dominant risk, has evolved as a distinct field of study and follow.

The dealing involves the insured forward a warranted and famous comparatively tiny loss within the kind of payment to the insurance company institution} in exchange for the insurer's promise to compensate (indemnify) the insured within the case of a financial (personal) loss. The insured receives a contract, referred to as the insurance, that details the conditions and circumstances underneath that the insured are going to be financially paid.

Benefits of Insurance
Insurance covers many risks and uncertainties in the world of business and act as a boon to the industrial or commercial concerns and general public. The following are some of the important services of insurance.
Risk Transfer : Businessman can easily and conviently transfer the risk of loss of insurance. It also safeguard the interest of individual and public.
Protection : Businessman do not have to worry about losses or damage when the risk of loss to their property is duly insured. They will receive compensation against actual loss their position becomes "as you were" even though the actual loss takes place. In life insurance , life policy give financial protection to the dependents to the extent of the assured who may be the only bread winner in the family.
Assured Profit : An insured businessman or policy holders can enjoy normal expected profits eg. 15% or 20% margin of profit.
Benefits to Consumers: As the property of the businessman is duly insured, and he can get a normal profit margin, he can charge lower prices to consumers.
Insurance Serves as a Basis of Credit : Insurance has the effect of improving credit standing of businessman, commercial banks and financial institutions insist for insurance of articles which are kept as security for loans. Life policy is a valuable asset and can raise an emergency loan against it.
Investment : A life insurance contract provides not only protection but also investment, or a pension in old age. Under life policy, one can also get bonuses added to the policy amount when we have with profit life policy.
Insurance encourages savings : Insurance is particularly true of life insurance. The insured person must save out of his current income an amount equal to the premium to be paid regularly and punctually. Thus, life insurance is a compulsory form of saving for the rainy day. For persons of limited means there is no other alternative substitute of savings.
Capital Formation : Insurance companies as institutional investors can mobilize small national savings in the form of insurance premia. They usually invest these funds in shares and debentures of business companies and also in government securities. This leads to faster capital formation.
Insurance offers many benefits to society : Some of the more important services offered by insurance to society in general are :
It creates confidence among the investing public.
It ensures security and safety.
It provides tax relief benefits.
It encourages provision for the future.
It leads to higher savings and investments.
It helps as uncertainty of business losses is reduced.
It attracts employees of better ability and caliber.
It enables small businesses to complete with large ones.
It provides maximum economic growth of the country.
It creates employment opportunities.
It ensures larger industrial development.
It can be used as a measuring rod during the period of inflation and deflation.


Types of Insurance

Sad eventualities such as loss of income, death, sickness, accidents, damage to property and many more are difficult to accurately predict. But thanks to insurance, you can cover possible unfortunate events so that when they happen you can conveniently restore status quo. Below is a list of common types of insurance:

Life Insurance – Pays out a specified figure to the insured or specified beneficiaries on a specific event such as death of the insured. [More: Types of Life Insurance]
Personal Accident Insurance – This will compensate you if at any single time an external violent event causes you disability, injury or death.
Medical and Health Insurance – You’ll need it to ascertain continued flow of income if you fall sick or get injured to the extent that you can’t work and earn as before. It also covers cost of medication, hospitalization and surgery. [More: Types of Health Insurance]
Vehicle Insurance – If you own a car, motor cycle or any other motor vehicle, this insurance covers it against accident or theft. A compressive package covers all possible losses as well as damages to third parties such as pedestrians. [More: Types of Car Insurance]
Home Insurance – Take this cover to insure your home against loss or damage as a result of fire, electricity fault, plumping malfunction, flood, etc.
Travel Insurance – When travelling alone or with your family, this cover ensures you’re compensated for any loss, damage, injury, sickness or inconvenience that comes up as a result. It may cover personal accidents, hijackings, travel delays and more.
Burial Insurance – This is a practical way to ease the burden of your funeral expenses on your family and the loved ones you leave behind in the unfortunate event of death. The cover addresses all your funeral costs.
Wedding Insurance – The cover comes in handy when certain aspects of your wedding go wrong. For instance, if a caterer you already paid goes out of touch when approaching the wedding day, the cover will provide an alternative.
Dog Bite Insurance – An aggressive dog may bite children, the elderly or even postal carriers within your home compound. Thus, you need this insurance to protect your assets if sued for dog bite.
Portable Electronic Device Insurance – This covers portable devices such as cell phones, laptops or tablets. The cover ensures replacement or repair of such devices if they’re stolen, lost or damaged.
Crime Insurance – This covers you or your business against loss or damage as a result of criminal acts of third parties. Covered risks include loss of funds through embezzlement by employees.
Political Risk Insurance – This cover protects your business against loss or damage arising from politically-related conditions such as civil unrest, coups, riots and revolutions.
Workers Compensation – An employer takes this policy on behalf of their employees to cover loss of income or medical expenses resulting from a work-related injury or sickness.
Disability Overhead Insurance – This is a cover against overhead expenses for business owners who are unable to work.
Aviation Insurance – This covers aircraft operations against aviation risks. Specific policies will offer compensation for damaged aircraft as well as cover third party liabilities such as injured or killed passengers, damaged crops or property etc.
Crop Insurance – If you’re a farmer, the cover protects you from losses associated with crop failure as a result of bad weather, infection or infestation.
Earth Quake Insurance – This is a good way to cover your home or property against loss or damage emanating from an earthquake.
Terrorism Insurance – The cover duly compensates you for loss or damage that results from acts of terrorism such as bombings or mass shootings.
Kidnap and Ransom Insurance – This cover comes to the rescue where ransom payment is necessary to secure the release of someone you love or associated with if they’re kidnapped, detained or hijacked.
Plant Insurance – This cover protects industrial equipment, machinery and plant such as tractors and earth movers against loss or damage.
Professional Liability Insurance – This protects professionals such as doctors and architects when their clients bring negligence claims against them.
Mortgage Insurance – The cover comes to the aid of a lender if a homebuyer defaults.

Importance of Insurance

Human beings, his family and properties are always exposed to different kinds of risks. Risk involve the losses. Insurance is a tool which reduces the cost of loss or effect of loss caused by variety of risk. It accumulates funds to meet individual losses. It is not device to prevent unwanted event of happening or cause of loss but protects them against that loss by compensating which as lost. The role and importance of insurance are discussed as follows:

1. Insurance provides security
Insurance provides safety and security against the loss on a particular event. Life insurance provides security against death and old age sufferings. Fire insurance protects against loss
due to fire while Marine insurance provides protection and safety against loss of ship and cargo. For personal accident and sickness insurance financial protection is given when the individual is unable to earn. In other insurance too, this security is provided against the loss at a given contingency.

2. Insurance reduces business risk or losses
In Business, commerce and industry, huge properties are employed. Because of slight negligence, the property may be turned in to ashes. A person may not be sure of his life, health and cannot continue the business up to the longer period to support his dependents. By the help of insurance, he can be sure of his earning, because the insurance company will pay a fixed amount at the time of death, damage by fire, theft, accident and other perils.

3. Insurance provides peace of mind
Insurance removes the tensions, fears, anxiety, frustrate or weaken of the human mind associated with the future uncertainty. By providing financial position and promise to compensate losses arise out from various risk, it provides peace of mind and stimulates more and better work performance of an individual.

4. Life insurance encourages saving
The insured has an obligation to pay premium regularly and cannot be withdrawn easily before the expiry of the term of policy. Life insurance encourages the habit of regular and systematic saving through premium and after a certain period, it would be a part of necessary saving of the insured person.

5. Insurance accelerates the economic growth of the country
To develop the economic growth of the country, insurance provides strong hand and mind, with protection against loss of property and capital to produce more wealth. It provides protection against different kinds of loss caused by risk. It accumulates the capital from the insured and utilizes for the development of country. Thus, the insurance meets all the requirements for the economic growth of a country.

6. Insurance provides credit facilities
The insured person can get loan by pledging insurance policy and the interest will not exceed the cash value of policy charged by insurer. In case of death of insured person, the policy can be utilized for setting of the loan with interest. Business person can take loan on the basis of insurance documents from the bank also.

7. Insurance helps to reduce inflation
Inflation created from over supply of money and on less production entities. Insurance can help to reduce the inflationary pressure in two ways. Firstly, it collects money as an amount of premium which controls over supply of money and secondly, it provides sufficient funds for increase production entities. Thus, it reduces the impact of inflation.

8. Insurance makes security and welfare of employees
The security and welfare of employees is the responsibility of employer. These security and welfare are easily met by life insurance, accident and sickness benefit and pension which are generally provided by group insurance. The premium for group insurance is normally paid by  
the employer. Insurance is the simple method for employer to fulfil their responsibility. Due to these benefits, employee will devote their maximum capacities to complete their job.

9. Other Importances  of Insurance
a) Insurance helps to promote foreign trade providing protection again trade risk.

b) Insurance increases business efficiency eliminating the loss of damage, destruction, or disappearance of property of goods.
c) Insurance protects the social wealth providing protection against social evil.
d) Development of insurance business helps to solve the evil of unemployment, generating employment opportunity in the country.
e) The insured gets tax benefit in life insurance.

Optimization of the high - risk surgical patient

Optimization   of   the  high -  risk  surgical   patient   the   use  of  ' goal - directed '  therapy

  In  the  1980s and  early  1990s, the treatment  of the critically ill  patient was seen to be becoming  increasingly  expensive with little  evidence that this expensive  care improved outcome. This applied particularly to surgical  patients in whom techniques  originally pioneered  in a healthy population  are  expanded to include  patients  who  are  more  elderly  with co- existing diseases.  These  high - risk  patients  have  a higher  mortality and  morbidity rate  and frequently  die  from  multiple  organ  dysfunction  syndrome (MODS), a syndrome  that  once  established  has proved largely resistant  to therapeutic  intervention . New  evidence  suggests  that  treatment  targeted towards  optimising cardiovascular function  might  improve  outcome.  To understand  the  principles involved, this  paper discusses normal physiological  changes around  the  time  of surgery, surgical mortality, and the pathophysiology of MODS,  before discussing  evidence  that  manipulating  cardiac function  to  increase  blood  flow  reduces  mortality  and  morbidity , this manipulation is known  generically as ' goal - directed' therapy .

PHYSIOLOGICAL   CHANGES  IN  THE  PERI - OPERATIVE  PERIOD


    IT  has been  known  for  some time  that there are changes in cardiovascular function  at the  time  of surgery .  In  patients  undergoing  thoracotomy,'  low cardiac index and  arterial  hypoxia  were  indicators  of non- survival  .  Following  the  development  of the  balloon- tipped , flow- directed pulmonary  artery  catheter, , it was  shown  that  patients  who  survived   major surgery  had higher cardiac index , lower  systemic  vascular  resistance, and  higher  oxygen delievery  than  non - survivors.  It was found  that the  commonly  monitored  vital  signs ( heart rate, temperature, central  venous pressure and  haemoglobin) were the  poorest  predictors  of  survival ,  while  perfusion- related variables ( such as oxygen  delievery and oxygen consumption ) and  cardiac  index ( which express  the interrelationship between  oxygen transport  and  red cell  volume and flow ) were  the best .  Furthermore , oxygen  transport values change  before the more  commonly monitored  variables ,  and , in patients  who die   or have  complications ,  vital signs usually  remain  in the  normal  range until the  terminal  event  , while oxygen  transport  variables  had started  to  change  some  hours  previously .
   It  has been  hypothesised  that  a  rise  in oxygen  transport   requirements  after  surgery  may  be  necessary  to  pay  back  an  oxygen  debt  that  has  accumulated  during  the  surgical  procedure.  Furthermore,  if  the cumulative  tissue  oxygen  debt  is calculated  during  the period  of operation,  it is found  that patients  who  survive have the smallest  oxygen  debt  and  patients who  fail  to survive have the  biggest; patients  with organ  failure  who  survive  have  intermediate  oxygen  debts.
In  summary  , cardiovascular changes  around  the  time  of surgery  produce  an  increase  in  tissue perfusion; if  this  compensatory  mechanism  fails, patients  are  more likely  to die and have  complications.

SURGICAL  MORTALITY  AND  MORBIDITY

   Assessing  mortality  rates  in  higher  risk  patients  is  difficult ; the  1991 Acute  Physiology  and  Chronic  Health  Evaluation  database  gives a 10.3%  mortality  for patients admitted directly  to  intensive   care from  the  operating  theatre  in  US  centres; in the  South  West Thames  ICU database  mortality  was  higher (9.4% for  elective surgery  and  28.7% for  emergency surgery  in  1993-1994), and  this is  similar  to  data  from  the Intensive  Care  National  Audit  and  Research  Council  database . Furthermore, the  National  Confidential  Enquiry  into  Peri- Operative Deaths  (NCEPOD )  in  England and  Wales  1992-1993 showed  that  the  median  day  of  death  was  day  6  and  that  patients  did  not  usually  die  soon  after  operation.  Postoperative   mortality  is  increased  in older  patients  with  pre- existing  disease   and  more  severe  surgery, and  this  has  recently  been  highlighted  by  the  Society  of  Cardiothoracic  Surgeons  of  Great  Britain  and  Ireland.  Studies  have  also  shown  that  thoracic and  abdominal  procedures  have  higher  mortality  and  complication  rates ; in elderly  patients  undergoing  non- cardiac surgery , mortality is  more  related  to  factors  such  as a history  of  cardiac  disease  and  signs  of  low  CI around  the  time  of  surgery  than  factors  such  as  the  type  of operation  performed.
    In  general, patients  with  non- elective  admissions ( mortality rate 30% versus  5%  for  elective admissions), ASA  grade 3+ (mortality rate 27% versus  8% for ASA <3 ), age  over 75 years ( mortality rate 20 % versus  11%  for  patients  aged  65-74 years )  and  major  surgery (mortality rate 25% versus 10 % for  non- major surgery) are  associated  with much  higher  mortality, and  these  factors are  more  important  than  the  type  of surgery.


MODS  AND  THE  SURGICAL  PATIENT


   A  syndrome  in which  there was multiple failure  of a number of organ systems was  first  described in the 1970s  in a group  of surgical  patients. This was initially  termed  multiple  organ  failure  syndrome (MOF) , but recently the  terminology has been  standardised and it is now called multiple organ  dysfunction syndrome (MODS).  MODS  carries a high mortality which increase  as the number of organ systems fail. The incidence  of MODS in surgical intensive care unit ( ICU) patients can be as high  as 44.3% , and is associated with prolonged illness , death and  increased  cost.  IT is currently estimated  that MODS accounts for 60-80% of all surgical  ICU death, and disappointingly there appears to have been little improvement  in prognosis of established  MODS over the last 20 years.

   There  are a number of factors which acting independently or in combination  trigger the onset of MODS but the final common pathway is that of cytokine activation; first a local production of cytokines in response to an injury or infection which  is a physiological  response , then a release of a small amount of cytokines into the body's circulation , and finally a massive systemic reaction where cytokines turn destructive by compromising the integrity of the capillary walls and flooding end-organs. The triggers that lead from a normal response to an unregulated pathological response probably involve genetic factors and the priming of the inflammatory system by other stimulants. One can imagine in the surgical situation  multiple stimulants to the inflammatory pathways been present in any one individual; these could include trauma, ischaemia, reperfusion injury, and  infective and chemical insults. One of the major factors intiating cytokine activation  appears to be alterations in microcirculatory flow, and others are related to tissue damage and the stimulation of inflammatoy mediators.  Shoemaker and colleagues reported the link between  failure of the normal postoperative responses of increased cardiac  index and oxygen delievery maintaining flow and perfusion , and the development of MODS  and death. This is probably the result of the activation of nuclear  factor-kB, but demonstrating this in humans undergoing surgery and then  relating this to the pathogenic processes of MODS and patient  outcome has been more complicated. However , the frequency  and magnitude of postoperative organ dysfunction after thoraco- abdominal aneurysm and abdominal aneurysm repair is associated with an increased concentration of the cytokines tumor necrosis factor-a and  interleukin -6 and this  is related to extended visceral ischaemia times.
 
   In summary , pathophysiological evidence  shows a direct link between surgery and trauma and the development of MODS in some patients; there is also an implication that the degree of surgery makes  this chain  of events  more  likely.  Moreover, evidence  above  suggests that  this is also more likely to occur when physiological  reserve  is limited