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Pancreatic Cancer
Dr.S.Sankar, MS, M.Ch
Surgical Gastroenterologist
Sri Ramachandra Medical
College
Chennai
Why Pancreas is a nemesis
Anatomical relations
Potent enzymes
Difficult to anastamose
Access
Cuddles the L Kidney
Tickles the Spleen
Hugs the Duodenum
Cradles the Aorta
Dallies with R Renal pedicle
Wraps the SMA
Opposes the IVC
Hides behind the peritonium
Incidence
Incidence
• Male : Female is 1.5:1
• Disease of old age. 80% of pancreatic
cancer occurs beyond the age of 60 years
• American Blacks-highest incidence (11-13
per 1,00,000)
Incidence
• In 2005, the American Cancer society
estimates that there will be approximately
32,180 new cases of pancreatic cancer in
the US, with 31,800 deaths
• Fourth most common cause of cancer
deaths
American cancer society. Cancer facts and figures
2005, Atlanta, GA
Ca Pancreas- The grim
situation
• Only 20% of pancreatic cancers are operable
for cure
• Only 10% - 15% of pancreatic cancers are alive
12 months after the diagnosis
• 5 year survival is less than 5%
• Average life of metastatic pancreatic cancer is 6
months
Etiology
• Cigarette smoking
• Diet – high fat and low fiber
• Diabetes
• Occupational
– benzidine
– naphthalimine
– Ethylene Dichloride
• Coffee – not proved
Etiology – Hereditary factors
Hereditary syndromes
– HNPCC
– PZ syndrome
– Ataxia Telangiectasia
– Hereditary Pancreatitis
– Familial Atypical Mole Melanoma syndrome
– FAP
Is Chronic Pancreatitis premalignant
• The incidence of pancreatic cancer in
various entities of chronic Pancreatitis are
as follows
– Hereditary Pancreatitis 25%
– Tropical Pancreatitis 10%
– Alcoholic Pancreatitis 5%
Oncogenes in pancreatic cancer
• K ras
• P 53
• P 16
• DPC 4
Pancreatic Neoplams
Primary Secondary
Exocrine Endocrine
Epithelial Mesenchymal
Ductal Acinar
Benign Intermediate Malignant
Solid Cystic
Ductal Adenocarcinoma
Periampullary
carcinoma
• Any tumor within 2
cm from the duodenal
papilla is defined as
periampullary cancer.
Ca terminal PD
Distal CBD
Ampullary tumor
Duodenal tumor
Site
• Pancreatic head-2/3rd
• Remaining part 1/3rd
Clinical presentation
• Mid epigastric pain radiating to back
• Weight loss
• Fatigue
• Anorexia
• Symptoms are vague and hence the
delayed presentation
Clinical presentation
• Painless progressive jaundice 50-60%
• Pruritus
• Staetorrhea
• Malabsorption
• New onset of Diabetes in older patients
Clinical presentation
• Jaundice is a late presentation in uncinate
process growth
• Severe back pain indicate irresectablity
and an omnious sign
Physical findings
• Palpable GB (Courvoisier’s law)
• Hepatomegaly
• Icterus
• Scratch marks
• Ascites
• Mass
• Virchow’s node
• Pelvic deposit
• Trousseau’s sign
Assessment
• Confirm the diagnosis
• Stage the disease
• Assess the operability
• General assessment for surgery
Investigation
• CBC
• LFT
• RFT
• Coagulation profile
• CXR
• ECG
• Echo
USG
• Cheap
• Level of obstruction
• Cause of obstruction
• Liver metastasis
• Ascites
USG
• Operator dependent
• Miss small metastasis
• Cannot assess operability
CT
• “Pancreatic protocol CT” is the gold
standard of investigation to stage the
disease and assess the operability
– Triple phase CT
– Closer cuts
– Water used as an intraluminal contrast
– Helical or multislice
“Operability is assessed in the office
of the surgeon and not in the
Operating room”
CT
• Advantages
– Available easily
– Surgeons are familiar with CT
– Excellent in giving details of operability
• Disadvantages
– May miss liver mets less than 1 cm
– Miss peritoneal mets
– Radiation
MRI
• Advantages
– No radiation
– Avoids contrast
– Single investigation that gives all the
information needed
• Disadvantages
– Cost & availability
– Surgeons are unfamiliar
MRI
ONE STOP SHOP
Role of Biopsy
Not mandatory
Why not a biopsy
• May upstage the disease
• Complications of biopsy
• Has a very low negative predictive value
Role of Biopsy
• Tissue diagnosis is indicated in cases which
are found inoperable by imaging
• Biopsy is indicated when Neoadjuvant
chemotherapy is planned
What biopsy
• Ideally it should be
done under EUS
guidance
– Targeted
– No tumor seeding
– No complications
like fistula
ERCP
Double duct sign
Not routinely done in
pancreatic
Cancer
Preop biliary drainage
Atypical lower CBD
obstruction
PET
• It is useful in differentiating pancreatic
cancer from chronic Pancreatitis
• Extra pancreatic disease
EUS
• Ideal method to evaluate
lower CBD obstruction
• Guided FNAC
• Vascular invasion
• EUS+FNAC= sensitivity of
90% and specificity of 95%
Angiography
No longer used
Barium studies – only historical
• Pad sign – widening of C loop
• Reverse 3 sign or Frostberg sign
Tumor markers
• CA 19-9
• CEA
• CA 125
• CA 50
• SPAN-1
• DUPAN-2
Staging
• TX primary tumor cannot be assessed
• T0 no evidence of primary tumor
• T1 confined to pancreas
T1a less than 2 cm
T1b more than 2 cm
• T 2 tumor extend to involve the bile
duct, duodenum and peripancreatic
tissue
• T3 involvement of stomach, spleen, colon,
vessels
Staging
• NX nodes cannot
be assessed
• N0 no evidence
of nodes
• N1 regional
nodes present
• MX cannot be
assessed
• M0 no metastasis
• M1 distant
metastasis
Stage grouping
• Stage I
– T1 N0 M0
– T2 N0 M0
• Stage II
– T3 N0 M0
• Stage III
– Any T N1 M0
• Stage IV
– Any T Any N M1
Prognosis
• Tumor size
• Node positivity
• Type of resection (R0 or R1)
• Ploidy
Operability
• Ca head 20%
• Ca body&tail 3%
• Ampullary 80%
Preop preparation
• Vitamin K
• Hydration
• Correction of electrolytes
• Preop nutrition
Surgery for pancreatic Ca
• Ca head Pancreaticoduodenectomy
• Ca body & Tail Distal Pancreatectomy
• Periampullary Pancreaticoduodenectomy
Attitude of the surgeon towards
pancreatic cancer
• Nihilistic
• Activist
• Realist
Pancreaticoduodenectomy
Pancreaticoduodenectomy offers the surgeon the only
chance to cure a patient with carcinoma of the head of
the pancreas and periampullary region
“Pancreaticoduodenecomy is the
Cadillac of operations”
but
“It is not a Cadillac that he ( surgeon)
is driving but a formula 1 Ferrari”
Sir Allen O Whipple
Pancreaticoduodenectomy
• Walter Kausch was the first to successfully
perform pancreaticoduodenectomy in Berlin
1912
• Allen Whipple popularized the operation in
US in 1935
• Now this operation is called Kausch-
Whipple procedure
Pancreaticoduodenectomy
• This operation suffered a very bad
reputation due to the operative mortality of
over 25% and morbidity of over 50%
• Some authorities have even suggested that,
this operation be abandoned
Pancreaticoduodenectomy –
consecutive series without mortality
J Howard-
41 cases
1968
J Cameron
145 cases
1993
Aranha
152 cases
2003
Michael Trede- 118 cases 1990
What made whipple safe
• Better surgical technique
• Anaesthesia
• Improvement in postoperative care
• Concept of high volume center and
clinical pathways
Pancreaticoduodenectomy
Despite the reduction in the operative
mortality to less than 5%, the morbidity
continues to be hovering around 40%
Whipple – 6 well defined operative steps
1. Cattle Brasch maneuver
2. Extended Kocherization
3. Portal Dissection, division
of Bile duct
4. Division of Stomach
5. Division of Jejunum
6. Pancreatic Neck
transection
Reconstruction after Classical Whipple’s operation
Hepaticojejunostomy
Gastrojejunostomy
Pancreaticojejunostomy
Pylorus preserving Pancreaticoduodenectomy
Total Pancreatectomy Reconstruction
Controversies
• Preop biliary drainage
• Preop imaging, CT vs. MR vs. EUS
• Role of biopsy
• Diagnostic laparoscopy
• PJ vs. PG
• Classical Whipple vs. PPPD
• Vascular resections
• Extended lymphadenectomy
• Drainage
Controversies
• Role of octreotide
• Order of reconstruction
• Adjuvant therapy
• Palliative resections
• Palliative bypass
Preop biliary drainage
• For
– Reduce the mortality and morbidity of surgery
– Improves the liver function
– Reduces the bleeding
– Improves the nutrition
– Buys time
Preop biliary drainage
• Against
– Does not reduce the mortality and morbidity
– More infectious complications
– It takes 6 weeks for the improvement of hepatic
microsomal functions
– Makes the duct small and fibrotic – adds to
technical difficulty
Preop biliary drainage
• Evidence
– Mc Pherson et al against
– Pitt et al against
– Hatfield et al against
– Lai et al against
– Lygitakis et al for
– Trede et al for
– Meta analysis against
Preop biliary drainage -
consensus
• Indicated
– Cholangitis
– Impending renal failure
– Surgery is likely to be delayed
– Bilirubin of more than 20 mg%
– Nutritionally very poor
– Neoadjuvant chemotherapy is planned
Preop biliary drainage -
consensus
Routine preop biliary
drainage is not
recommended and there is
no evidence to support it
Diagnostic laparoscopy
• 30% of patients found operable by imaging
are found to have small liver mets or
peritoneal mets, on diagnostic laparoscopy
Warshaw et al
Diagnostic laparoscopy
With the advent of high
quality CT, Helical and
Multislice, occult peritoneal
and liver metastasis are
documented in only 10% in
some series
PJ vs. PG
• Merits of PG
– Stomach is in proximity to pancreatic stump
– Better vascularity
– Acid in stomach inactivates enzymes
– Absence of enterokinase
– Even if leak occurs the enzymes are not
activated and hence fatal bleeding do not occur
PJ vs. PG
• Two randomized controlled trials fail to
demonstrate superiority of one method over
the other
• Dilated duct, texture of pancreas and
surgeon’s experience are more important
than the viscera used for drainage
Classical Vs PPPD
• PPPD is oncologically as radical as classical
whipple except for tumors encroaching on
the D1 and pylorus
• RCTs have failed to show any significant
benefit of PPPD over classical whipple
Vascular
involvement
• Resection of SMV is
accepted provide it
enables to perform R0
resections
• Involvement of SMA is
a contraindication for
resection
Extended
lymphadenectomy
• Studies have shown that
extended
lymphadenectomies can
be done with acceptable
morbidity
• Extended
lymphadenectomy do not
improve the survival
Octreotide
• There have been totally six RCT across the
Atlantic, three from Europe ( Buchler et al, Beger
et al , Pedrazolli et al) and three from US ( Yeo et
al, Sarr et al and Lowy et al)
• The European trials favor use of octreotide and the
American trials do not favor
• Recently published meta analysis of these trials
have shown a benefit of octreotide in reducing the
complications
Adjuvant therapy
• Chemotherapy
• Radiotherapy
• Chemo radiotherapy
Adjuvant therapy
• The ESPAC trial has shown that the only
factor that positively affect the long term
survival is administration of adjuvant
chemotherapy
• Ideally all patients undergoing surgery for
cancer pancreas should be given adjuvant
chemotherapy
Palliative resections – Is it
acceptable
Palliation
• Jaundice (pruritus)
• Duodenal obstruction
• Pain
• Bleeding
Palliative bypass
• Options of by-pass
– Choledochojejunostomy ( Loop or Roux en Y)
– Cholecystojejunostomy
– Hepaticojejunostomy
Palliative bypass-prophylactic GJ
• The current recommendation is to perform
a prophylactic GJ along with the biliary
bypass even if there is no gastric outlet
obstruction
Laparoscopy in palliation
• Depending on the expertise of the surgeon,
procedures can be done with laparoscopy
Palliation of pain
• Neurolysis ( 20 ml of absolute alcohol
injected on either side of the celiac axis to
destroy the celiac ganglia)
– At laparotomy
– CT guided
– EUS guided
– Thoracoscopic splanchnectomy
Surgery has reached the zenith
Thank You

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Pancreatic Cancer.ppt

  • 2. Dr.S.Sankar, MS, M.Ch Surgical Gastroenterologist Sri Ramachandra Medical College Chennai
  • 3. Why Pancreas is a nemesis Anatomical relations Potent enzymes Difficult to anastamose Access
  • 4. Cuddles the L Kidney Tickles the Spleen Hugs the Duodenum Cradles the Aorta Dallies with R Renal pedicle Wraps the SMA Opposes the IVC Hides behind the peritonium
  • 6. Incidence • Male : Female is 1.5:1 • Disease of old age. 80% of pancreatic cancer occurs beyond the age of 60 years • American Blacks-highest incidence (11-13 per 1,00,000)
  • 7. Incidence • In 2005, the American Cancer society estimates that there will be approximately 32,180 new cases of pancreatic cancer in the US, with 31,800 deaths • Fourth most common cause of cancer deaths American cancer society. Cancer facts and figures 2005, Atlanta, GA
  • 8. Ca Pancreas- The grim situation • Only 20% of pancreatic cancers are operable for cure • Only 10% - 15% of pancreatic cancers are alive 12 months after the diagnosis • 5 year survival is less than 5% • Average life of metastatic pancreatic cancer is 6 months
  • 9. Etiology • Cigarette smoking • Diet – high fat and low fiber • Diabetes • Occupational – benzidine – naphthalimine – Ethylene Dichloride • Coffee – not proved
  • 10. Etiology – Hereditary factors Hereditary syndromes – HNPCC – PZ syndrome – Ataxia Telangiectasia – Hereditary Pancreatitis – Familial Atypical Mole Melanoma syndrome – FAP
  • 11. Is Chronic Pancreatitis premalignant • The incidence of pancreatic cancer in various entities of chronic Pancreatitis are as follows – Hereditary Pancreatitis 25% – Tropical Pancreatitis 10% – Alcoholic Pancreatitis 5%
  • 12.
  • 13. Oncogenes in pancreatic cancer • K ras • P 53 • P 16 • DPC 4
  • 14. Pancreatic Neoplams Primary Secondary Exocrine Endocrine Epithelial Mesenchymal Ductal Acinar Benign Intermediate Malignant Solid Cystic Ductal Adenocarcinoma
  • 15. Periampullary carcinoma • Any tumor within 2 cm from the duodenal papilla is defined as periampullary cancer. Ca terminal PD Distal CBD Ampullary tumor Duodenal tumor
  • 16.
  • 17. Site • Pancreatic head-2/3rd • Remaining part 1/3rd
  • 18. Clinical presentation • Mid epigastric pain radiating to back • Weight loss • Fatigue • Anorexia • Symptoms are vague and hence the delayed presentation
  • 19. Clinical presentation • Painless progressive jaundice 50-60% • Pruritus • Staetorrhea • Malabsorption • New onset of Diabetes in older patients
  • 20. Clinical presentation • Jaundice is a late presentation in uncinate process growth • Severe back pain indicate irresectablity and an omnious sign
  • 21. Physical findings • Palpable GB (Courvoisier’s law) • Hepatomegaly • Icterus • Scratch marks • Ascites • Mass • Virchow’s node • Pelvic deposit • Trousseau’s sign
  • 22. Assessment • Confirm the diagnosis • Stage the disease • Assess the operability • General assessment for surgery
  • 23. Investigation • CBC • LFT • RFT • Coagulation profile • CXR • ECG • Echo
  • 24. USG • Cheap • Level of obstruction • Cause of obstruction • Liver metastasis • Ascites
  • 25. USG • Operator dependent • Miss small metastasis • Cannot assess operability
  • 26. CT • “Pancreatic protocol CT” is the gold standard of investigation to stage the disease and assess the operability – Triple phase CT – Closer cuts – Water used as an intraluminal contrast – Helical or multislice
  • 27.
  • 28.
  • 29. “Operability is assessed in the office of the surgeon and not in the Operating room”
  • 30. CT • Advantages – Available easily – Surgeons are familiar with CT – Excellent in giving details of operability • Disadvantages – May miss liver mets less than 1 cm – Miss peritoneal mets – Radiation
  • 31. MRI • Advantages – No radiation – Avoids contrast – Single investigation that gives all the information needed • Disadvantages – Cost & availability – Surgeons are unfamiliar
  • 33. Role of Biopsy Not mandatory
  • 34. Why not a biopsy • May upstage the disease • Complications of biopsy • Has a very low negative predictive value
  • 35. Role of Biopsy • Tissue diagnosis is indicated in cases which are found inoperable by imaging • Biopsy is indicated when Neoadjuvant chemotherapy is planned
  • 36. What biopsy • Ideally it should be done under EUS guidance – Targeted – No tumor seeding – No complications like fistula
  • 37. ERCP Double duct sign Not routinely done in pancreatic Cancer Preop biliary drainage Atypical lower CBD obstruction
  • 38. PET • It is useful in differentiating pancreatic cancer from chronic Pancreatitis • Extra pancreatic disease
  • 39. EUS • Ideal method to evaluate lower CBD obstruction • Guided FNAC • Vascular invasion • EUS+FNAC= sensitivity of 90% and specificity of 95%
  • 41. Barium studies – only historical • Pad sign – widening of C loop • Reverse 3 sign or Frostberg sign
  • 42. Tumor markers • CA 19-9 • CEA • CA 125 • CA 50 • SPAN-1 • DUPAN-2
  • 43. Staging • TX primary tumor cannot be assessed • T0 no evidence of primary tumor • T1 confined to pancreas T1a less than 2 cm T1b more than 2 cm • T 2 tumor extend to involve the bile duct, duodenum and peripancreatic tissue • T3 involvement of stomach, spleen, colon, vessels
  • 44. Staging • NX nodes cannot be assessed • N0 no evidence of nodes • N1 regional nodes present • MX cannot be assessed • M0 no metastasis • M1 distant metastasis
  • 45. Stage grouping • Stage I – T1 N0 M0 – T2 N0 M0 • Stage II – T3 N0 M0 • Stage III – Any T N1 M0 • Stage IV – Any T Any N M1
  • 46. Prognosis • Tumor size • Node positivity • Type of resection (R0 or R1) • Ploidy
  • 47. Operability • Ca head 20% • Ca body&tail 3% • Ampullary 80%
  • 48. Preop preparation • Vitamin K • Hydration • Correction of electrolytes • Preop nutrition
  • 49. Surgery for pancreatic Ca • Ca head Pancreaticoduodenectomy • Ca body & Tail Distal Pancreatectomy • Periampullary Pancreaticoduodenectomy
  • 50. Attitude of the surgeon towards pancreatic cancer • Nihilistic • Activist • Realist
  • 51. Pancreaticoduodenectomy Pancreaticoduodenectomy offers the surgeon the only chance to cure a patient with carcinoma of the head of the pancreas and periampullary region
  • 52. “Pancreaticoduodenecomy is the Cadillac of operations” but “It is not a Cadillac that he ( surgeon) is driving but a formula 1 Ferrari”
  • 53. Sir Allen O Whipple
  • 54. Pancreaticoduodenectomy • Walter Kausch was the first to successfully perform pancreaticoduodenectomy in Berlin 1912 • Allen Whipple popularized the operation in US in 1935 • Now this operation is called Kausch- Whipple procedure
  • 55. Pancreaticoduodenectomy • This operation suffered a very bad reputation due to the operative mortality of over 25% and morbidity of over 50% • Some authorities have even suggested that, this operation be abandoned
  • 56. Pancreaticoduodenectomy – consecutive series without mortality J Howard- 41 cases 1968 J Cameron 145 cases 1993 Aranha 152 cases 2003 Michael Trede- 118 cases 1990
  • 57. What made whipple safe • Better surgical technique • Anaesthesia • Improvement in postoperative care • Concept of high volume center and clinical pathways
  • 58. Pancreaticoduodenectomy Despite the reduction in the operative mortality to less than 5%, the morbidity continues to be hovering around 40%
  • 59. Whipple – 6 well defined operative steps 1. Cattle Brasch maneuver 2. Extended Kocherization 3. Portal Dissection, division of Bile duct 4. Division of Stomach 5. Division of Jejunum 6. Pancreatic Neck transection
  • 60. Reconstruction after Classical Whipple’s operation Hepaticojejunostomy Gastrojejunostomy Pancreaticojejunostomy
  • 63. Controversies • Preop biliary drainage • Preop imaging, CT vs. MR vs. EUS • Role of biopsy • Diagnostic laparoscopy • PJ vs. PG • Classical Whipple vs. PPPD • Vascular resections • Extended lymphadenectomy • Drainage
  • 64. Controversies • Role of octreotide • Order of reconstruction • Adjuvant therapy • Palliative resections • Palliative bypass
  • 65. Preop biliary drainage • For – Reduce the mortality and morbidity of surgery – Improves the liver function – Reduces the bleeding – Improves the nutrition – Buys time
  • 66. Preop biliary drainage • Against – Does not reduce the mortality and morbidity – More infectious complications – It takes 6 weeks for the improvement of hepatic microsomal functions – Makes the duct small and fibrotic – adds to technical difficulty
  • 67. Preop biliary drainage • Evidence – Mc Pherson et al against – Pitt et al against – Hatfield et al against – Lai et al against – Lygitakis et al for – Trede et al for – Meta analysis against
  • 68. Preop biliary drainage - consensus • Indicated – Cholangitis – Impending renal failure – Surgery is likely to be delayed – Bilirubin of more than 20 mg% – Nutritionally very poor – Neoadjuvant chemotherapy is planned
  • 69. Preop biliary drainage - consensus Routine preop biliary drainage is not recommended and there is no evidence to support it
  • 70. Diagnostic laparoscopy • 30% of patients found operable by imaging are found to have small liver mets or peritoneal mets, on diagnostic laparoscopy Warshaw et al
  • 71. Diagnostic laparoscopy With the advent of high quality CT, Helical and Multislice, occult peritoneal and liver metastasis are documented in only 10% in some series
  • 72. PJ vs. PG • Merits of PG – Stomach is in proximity to pancreatic stump – Better vascularity – Acid in stomach inactivates enzymes – Absence of enterokinase – Even if leak occurs the enzymes are not activated and hence fatal bleeding do not occur
  • 73. PJ vs. PG • Two randomized controlled trials fail to demonstrate superiority of one method over the other • Dilated duct, texture of pancreas and surgeon’s experience are more important than the viscera used for drainage
  • 74. Classical Vs PPPD • PPPD is oncologically as radical as classical whipple except for tumors encroaching on the D1 and pylorus • RCTs have failed to show any significant benefit of PPPD over classical whipple
  • 75. Vascular involvement • Resection of SMV is accepted provide it enables to perform R0 resections • Involvement of SMA is a contraindication for resection
  • 76. Extended lymphadenectomy • Studies have shown that extended lymphadenectomies can be done with acceptable morbidity • Extended lymphadenectomy do not improve the survival
  • 77. Octreotide • There have been totally six RCT across the Atlantic, three from Europe ( Buchler et al, Beger et al , Pedrazolli et al) and three from US ( Yeo et al, Sarr et al and Lowy et al) • The European trials favor use of octreotide and the American trials do not favor • Recently published meta analysis of these trials have shown a benefit of octreotide in reducing the complications
  • 78. Adjuvant therapy • Chemotherapy • Radiotherapy • Chemo radiotherapy
  • 79. Adjuvant therapy • The ESPAC trial has shown that the only factor that positively affect the long term survival is administration of adjuvant chemotherapy • Ideally all patients undergoing surgery for cancer pancreas should be given adjuvant chemotherapy
  • 80. Palliative resections – Is it acceptable
  • 81. Palliation • Jaundice (pruritus) • Duodenal obstruction • Pain • Bleeding
  • 82. Palliative bypass • Options of by-pass – Choledochojejunostomy ( Loop or Roux en Y) – Cholecystojejunostomy – Hepaticojejunostomy
  • 83. Palliative bypass-prophylactic GJ • The current recommendation is to perform a prophylactic GJ along with the biliary bypass even if there is no gastric outlet obstruction
  • 84. Laparoscopy in palliation • Depending on the expertise of the surgeon, procedures can be done with laparoscopy
  • 85. Palliation of pain • Neurolysis ( 20 ml of absolute alcohol injected on either side of the celiac axis to destroy the celiac ganglia) – At laparotomy – CT guided – EUS guided – Thoracoscopic splanchnectomy
  • 86. Surgery has reached the zenith