Basic Science: Stomach

Grace Kim, MD May 23, 2007

Essential Anatomy

Beware: Aberrant L hepatic artery

• Parietal cell – BODY – Acid – Intrinsic Factor • Mucus – BODY/ANTRUM – Mucus • Chief – BODY – Pepsin

• G – ANTRUM – Gastrin • D – BODY/ANTRUM – Somatostatin • Surface epithelial – DIFFUSE – Mucus – Bicarb – ?Prostaglandin

GI Hormones

• Gastrin – Antral G cells  • Cholecystokinin - duo  increase acid GB contraction, pancreatic secretion • Secretin – duo S cells  bicarb release, pancreatic secretion • Glucagon – panc α cells  • VIP – gut peptide  increase gluc release SM relaxation, increase gut secretion • Gastric inhibitory peptide = glucose insulinotropic – K cells of gut • Somatostatin – gut   induce insulin secretion global gut inhibition • Motilin – Mo cell of SB  upregulate MMC • Peptide YY – gut  • Neurotensin – SB  global inhibition bicarb release, decrease gastric motility

Benign Diseases of the Stomach

• Case: 80 yo woman with HTN and CAD is admitted with SBO. NGT decompression is initiated. – Is GI prophylaxis necessary? If yes, what kind?

– What are we prophylaxing against?

Stress Gastritis

• Develops within 48 hrs of stress • Clinically-significant bleeding uncommon – 4% with risk factor, 0.1% without

Cook DJ, et al: Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 330:377-381, 1994

Stress Gastritis

• Prophylaxis for critically-ill: – Mechanical vent > 48hrs – Coagulopathy – Spinal cord injury – Prior history of therapy – History of GI bleed

• +/- indications in the critically-ill – MODS – Cirrhosis – CNS injury – Steroids – Pressors – Multiple organ injuries • General medical population – Data is sparse!

Treatment of Bleeding Stress Gastritis

– Endoscopy • Coagulation • Injection – Interventional • Embolization • Selective vasopressin infusion – Surgical • Oversewing • Wedge resection • Total devascularization and vagotomy – Mucosal ischemia common, perforation uncommon • Total gastrectomy last resort

Peptic Ulcer Disease

• Treated medically in most cases • Elective surgery rare • Emergency surgery still common – 130,000 cases/year – 9000 patient deaths/year

• GASTRIC ULCER • 4 types, varying etiologies • 75% HP • NSAID history more common • Usually older patients • DUODENAL ULCER • Usually associated with excess acid production • 90% HP

Type 1 Type 2 Type 3 Type 4

H. pylori

• Gram negative rod • Produces urease (splits urea into ammonium and bicarb) • Injury – Local toxins – Tissue immune response – Gastrin production • 98% success in preventing recurrence if organism eradicated (vs. 75% without)

Tests for H. pylori

• Serology (90% sens/spec, + for > 1 yr) • Urea breath test (95% sens/spec) • Rapid urease test (90% sens/98% spec) • Histology (95% sens/98% spec) • Culture (to determine sensitivity to Abx)

Pathogenesis

• Imbalance between acid secretion and mucosal defense • “No acid, no ulcer” • “No acid, no Factor X, no ulcer” • Factor X =

H. pylori

, cigarette smoking, NSAIDs, steroids

• Case: 50 yo man, a smoker, with lower back pain on NSAIDs has an outpatient EGD for chronic melena. EGD demonstrates a 1 cm non-bleeding gastric ulcer in the body. -Management?

Medical Treatment

• Stop NSAIDs • Stop smoking • Treat H. pylori – Triple therapy (OAC, OMC, OAM) x 1 week, PPI x 2 weeks – Success 90-95% • PPI (96% ulcer healing at 8 weeks) • Gastric ulcers: need rescope 8-12 weeks

• Case: 77 yo woman in the MICU is found to have a 5 cm gastric ulcer located along the lesser curvature. Multiple biopsies are taken which come back as chronic inflammatory tissue. She is on a PPI.

– Management?

Gastric ulcer: elective surgery

• Intractable ulcer – Persist despite adequate treatment (3 mos) – Recurs within 1 yr despite maintenance therapy – Cycle of recurrence/remissions – Cannot rule out malignancy – ZE has been ruled out • Giant gastric ulcer (> 3cm) • OPERATION = Resection with reconstruction +/ vagotomy – Vagotomy for Type 2/3

Billroth reconstructions

Roux-en-Y reconstruction

Duodenal ulcer: elective surgery

• Intractable ulcer – Very rare • Antrectomy or distal gastrectomy with truncal vagotomy

Vagotomies

• Truncal vagotomy • Selective vagotomy (not done any more) • Highly selective = parietal cell = proximal gastric vagotomy

PUD: Emergent Surgical Indications

• Hemorrhage  oversew/excise/resect – Don’t forget to biopsy gastric ulcers • Perforation  patch/excise/resect – Don’t forget to biopsy gastric ulcers • Obstruction  resect • Consider vagotomy if stable and HP(-), with recalcitrant disease, or NSAID dependent

• Case: 30 yo otherwise healthy woman on no medications presents with peritonitis. On laparoscopy, you find a perforated duodenal ulcer.

• Management?

• Graham patch • If known H. pylori negative – consider vagotomy and pyloroplasty • PPI, HP treatment if positive

• Case: 65 yo man on NSAIDs for chronic lower back pain, smoker presents with hematemesis. On endoscopy, he has a gastric ulcer along the lesser curvature with a visible bleeding vessel. Heater probe is unsuccessful. • Management?

• OR • Gastrotomy – biopsy ulcer, oversew ulcer • Stop NSAIDs • Start PPI • Stop smoking • Test for H. pylori, treat if (+) • No vagotomy necessary • Rescope 8-12 weeks to document healing

• Case: 80 yo woman in MICU with bleeding duodenal ulcer, Hct 23 after 4U PRBCs. • Management?

• OR • Open pylorus • 3-point vessel ligation • Pyloroplasty • Vagotomy if stable • PPI, test for H. pylori

• Case: 60 yo woman with long-standing history of PUD on multiple courses of PPI presents with chronic gastric outlet obstruction. H. pylori negative. Endoscopy demonstrates a pan-gastritis and a bulky antral ulcer. The scope cannot be passed into the duodenum.

• Management?

• Hydrate, correct electrolytes • NGT decompression • Hyperalimentation or jejunal feeds • PPI • Antrectomy with BI with TV

• Case: The duodenum is stuck down and cannot be mobilized up for a BI. You proceed with a BII, however, it appears that your duodenal staple line is dehiscing.

• Management?

Difficult Duodenal Stump

• Extra caution that the afferent loop is totally patent • Buttress staple line with omentum • Decompress afferent loop with Levin tube • Lateral tube duodenostomy or retrograde jejunostomy • Drain widely • Leak mortality: 30 – 50%

Post-gastrectomy Issues

• Case: Your 70 yo woman who underwent a subtotal gastrectomy with Roux-en-Y for ulcer disease is recovering well. What supplements should she be placed on?

Metabolic Disturbances

• Anemia – Iron-deficiency – B12-deficiency • Impaired fat absorption – Fat-soluable vitamins (esp. Vit D) • Impaired calcium absorption

• Case: You perform a truncal vagotomy and antrectomy with BII reconstruction for a 65 yo man with intractable ulcer disease. He begins to have severe pain in the RUQ on POD#5. CT demonstrates a large RUQ collection.

Early Post-gastrectomy problems

• Leak at GJ, JJ (Roux-en-Y), or duodenal stump – Pain, fever, leukocytosis, biliary output from drains  reoperate • Anastomotic bleed  EGD • Obstruction  trial of conservative management, re-operate • Delayed gastric emptying  conservative mangement and promotility agents

• Case: 80 yo man undergoes subtotal gastrectomy with Roux-en-Y for gastric cancer. He presents to your office with severe cramping, diaphoresis, and diarrhea after he eats.

• Diagnosis?

• Management?

Late Post-gastrectomy problems

• Dumping – Early: Diaphoresis, weakness, tachycardia 15 minutes after a meal – Late: Hypoglycemia 2 hours after meal – Etiology: Loss/bypass of pyloric sphincter, hormonal aberrations (VIP, cholecystokinin, neurotensin, peptide YY)

Dumping Syndrome

• Medical management – Avoid sugars, carbs – Small, frequent meals with high protein, fat – Fiber – No liquids while eating – Octreotide • Surgery = the last resort 1% – Isoperistaltic loop – Long-limb Roux-en-Y

Late Post-gastrectomy problems

• Diarrhea – Medical management – Isoperistaltic loop as last resort • Recurrent peptic ulcer – DDx: incomplete vagotomy, retained antrum, ZE, gastric stasis, NSAIDs, H. pylori infection, gastric cancer

Recurrent Peptic Ulcer

• EGD: biopsy to r/o cancer, H. pylori • Gastrin level and basal acid output: to evaluate for ZE and retained antrum • Secretin stimulation test: ZE vs. retained antrum • Check path report: incomplete vagotomy?

Recurrent Peptic Ulcer

• Manage conservatively • Operate for bleeding, perforation, obstruction, and “intractability” • Operation: Step up from what was originally done – PCV  V and P – V and P  V and A – Subtotal gastrectomy  total gastrectomy – Consider thoracosopic truncal vagotomy

Late Post-gastrectomy problems

• Gastroparesis – Loss of antral pump with vagotomy – Rule out mechanical obstruction – Treatment: Dietary modification, promotility agents – Surgery as last resort: Near total with Roux en-Y

Late Post-gastrectomy problems

• Bile reflux Gastritis – Workup: HIDA, EGD – No good medical treatment – Convert BII to long-limb RY (40-50 cm) • Roux syndrome – Impaired gastric empyting without obstruction – Medical management – Last resort: Near-total gastrectomy with new Roux limb

• Case: 40 yo woman 7 days after Roux-en Y gastric bypass has LUQ/epigastric pain and nausea. Patient has a palpable tender mass in the LUQ. CT demonstrates a dilated gastric remnant and duodenum.

• Diagnosis?

• Management?

Late Post-gastrectomy problems

• Afferent Loop Obstruction – Pain after eating, relieved by projectile bilious emesis – Acute or chronic – Etiology: Adhesions, stenosis, volvulus, afferent limb too long – Treatment: Surgery (adhesiolysis, shorten afferent limb, convert BII to RY)

Other Gastric Pathology

• Case: 45 yo woman with long history of PUD on PPI presents with diarrhea epigastric pain. On endoscopy she is found to have multiple ulcers throughout her stomach.

• Diagnosis?

• Treatment?

Zollinger-Ellison Syndrome

• Presentation: Abdominal pain, PUD, esophagitis • Atypical PUD – Ulcers in atypical locations (distal duo/jej) – Multiple ulcers – Failure to respond to conventional treatment – Ulcers with diarrhea

ZE

• Dx – Serum gastrin level >1000 pg/ml diagnostic (off PPI) – Secretin-stimulation: check gastrin at 2,5,10, 15, 30 minutes; increase more than 200 pg/ml diagnostic – DDX of hypergastrinemia: PPI, renal failure, G-cell hyperplasia, atrophic gastritis, retained or excluded antrum, gastric outlet obstruction

ZE

• Rule out MEN I (PPP) – Check serum calcium and PTH levels • MEN I (25%) – Do total parathyroidectomy first – Medical management for metastatic gastrinoma – debulking has not been shown to enhance survival – Possible surgery for isolated gastrinoma

ZE: Gastrinoma Triangle

• 70-90% located in triangle • Junction of cystic duct/CBD • 2 nd /3 rd portion of duodenum • Neck/body of pancreas

ZE: Tumor localization

• Octreotide scan (85% sens) • Endoscopic ultrasound • CT scan

Treatment

• PPI • Surgery for resection – Explore to find tumor and determine resectability – Local resection with lymphadectomy of nodes in gastrinoma triangle – Unresectable or gastrinoma cannot be identified: PCV

• Case: On laparotomy for a patient with a gastrinoma localized by octreotide scan, you cannot find the tumor.

• What are your options?

Adjuncts to find gastrinoma

• Intraoperative ultrasound to examine duo, pancreas, liver • Intraoperative EGD • Transillumination with EGD • Duodenotomy in proximal duo – palpate wall

ZE: Postop considerations

• Follow patient with gastrin, calcium and PTH levels and octreotide scans • Chemo: streptozocin, doxorubicin, 5-FU • Prognosis: 15-yr without liver mets 80%, 5-yr with liver mets 20-50%

• Case: 40 yo woman with DM, HTN, sleep apnea, chronic lower back pain, and arthritis who weighs 235 lbs and is 5’4” with a BMI of 40 presents to you. She is interested in weight-loss options.

A few words on bariatric surgery…

• NIH Guidelines – BMI > 40; or BMI > 35 with comorbidities – Failed previous attempts at nonsurgical weight loss – No active history of alcohol or substance abuse or uncontrolled psychiatric disease – Realistic expectations and commitment to followup – Acceptable risk for surgery

VBG

• 40-50% EBW loss over 1-2 yrs • Pouch dilatation, staple line disruption, band migration, band obstruction common • Reop rate 30%

Gastric Bypass

• 60-70% EBW loss over two years

Lap Adjustable Band

• Allergan band FDA approved in 2002 • 40-50% EBW over 3 5 years • Complications: band slippage, erosion • Reop rate 10%

Biliopancreatic Diversion

• Distal gastrectomy • Short common channel  50 cm • 80% EBW lost • Potential complications: severe protein-calorie malnutrition, fat-soluble vitamin deficiency, diarrhea, **marginal ulcers

Duodenal Switch

• Pylorus is preserved • Can be 1- or 2- stage • Start with sleeve gastrectomy • Good for patients with scarring at GEJ

Gastric Neoplasms

• Case: 74 yo African-American man, smoker, who used to work in a coal mine 40 years ago, presents with epigastric pain and weight loss. • Workup?

Gastric Cancer

• 10 th most common malignancy in US – More common in males, African-Americans, Hispanics, Native Americans • 2 nd most common malignancy in world (after lung) – 75-100/100,000 in parts of Asia – 8-15/100,000 in US

Pathology

• 95% of US variety: adenocarcinoma • Lauren classification – Intestinal • Assoc with chronic H. pylori infection, gastritis • Glandular • Distal stomach more commonly affected • Hematogenous spread – Diffuse • Poorly-differentiated • Arise from lamina propria, usu prox stomach • Lymphatic spread, early metastasis • Most commonly located on lesser curvature

Risk Factors

• Diet (smoked foods, low in fruits/veggies) • Smoking • Male gender • African-American race • Low socioeconomic status • Occupational hazards (metal, rubber) • H. pylori infection • Adenomatous polyps • EBV • HNPCC

• Presentation – Abdominal pain – Weight loss – Chronic blood-loss anemia • Diagnosis – EGD – Staging: CXR and CT abdomen/pelvis, consider EUS, diagnostic laparoscopy

Staging

• AJCC/UICC Staging system • T1-4 (submucosa-muscularis propria serosa-adjacent organs) • N0-3 (none, 1-6, 7-15, >15) – Need at least 15 nodes to N stage • Stage 1 (T1N0-1 or T2N0), Stage 2 (T1N2, T2N1, T3N0), Stage 3 (T1-3N1-2, T4N0), Stage 4 (T4N1-3, etc.)

• Case: The patient has a 5 cm fungating antral mass which is adenocarcinoma on biopsy. On ultrasound it appears to be a T3 lesion.

• Management?

R Status

• R0 – microscopically-negative margin • R1 – macroscopically-negative margin • R2 – gross residual disease

Surgical Treatment

• Resection with en-bloc lymphadenectomy – 6 cm margin ideal • Proximal tumors: total gastrectomy or esophagogastrectomy • Midbody tumors: total gastrectomy • Distal tumors: distal subtotal gastrectomy • Local en-bloc organ resection only done to perform R0 resection

D Status

• Extent of LN dissection • D1 – only perigastric nodes • D2 – perigastric, hepatic, L gastric, celiac, splenic, and perigastric nodes > 3 cm away from primary tumor • D3 – D2 plus porta hepatis, retropancreatic, and paraaortic nodes

• Case: Will you do a D1, D2, or D3 dissection?

Lymphadenectomy

• 5 prospective-randomized trials – South African trial: no benefit – Dutch trial: no benefit, more morbid – MRC trial: no benefit – Hong Kong trial: improved survival D3 – JCOG: overall mortality 1% for D2 or D3 • No definite consensus • D2 dissections considered investigational in USA

Treatment

• Adjuvant: Chemo/XRT (5-FU/leucovorin, XRT) • Neoadjuvant: investigational • Palliative: resection, bypass, chemo/RT, laser recanalization, dilation, stents

Prognosis

• Overall 5-yr survival 10-21% • Recurrence 40-80% (usu. In first 3 yrs)

Gastric Lymphoma

• Stomach: most common location for GI lymphoma • RX: Chemo/XRT (controversial) • MALToma: treat H. pylori

• Case: 50 yo woman complains of early satiety. CT of the abdomen/pelvis demonstrates a 5-cm well-circumscribed, vascular mass abutting the posterior stomach in the lesser sac.

• Diagnosis?

• Treatment?

Gastric GIST

• 65% stomach, 25% small intestine • Symptoms related to compression/displacement • Radiologically-unique: vascular, well circumscribed, closely-associated with the stomach on CT; intense uptake on FDG PET • Bx not indicated (unless r/o lymphoma)

Genetics

• C-kit proto-oncogene encodes KIT protein – Trans-membrane receptor tyrosine kinase • KIT gene mutation in 75-90% of GISTs • STI571 (Gleevac) selectively inhibits tyrosine kinases • Response rate of 60% to Gleevac in metastatic GIST

Treatment

• Surgical resection: segmental en-bloc resection with negative margins • Prognostic factors – Size – Histology (>5 mitoses/50 HPF) – Tumor location • Follow with serial CT • Gleevac only FDA-approved for recurrent/metastatic disease, other use in setting of clinical trial

Recurrent GIST

• Gleevac • Conventional chemo • Consider surgery

Other Benign Pathologies

• Case: 18 yo college student has multiple episodes of hematemesis after binge drinking.

• DDx?

• Management?

Mallory-Weiss

• Etiology of UGI in 5-15% cases • Pathophysiology: acute increase in intraabdominal pressure – Forceful emesis – CPR – Blunt trauma – Childbirth – Straining for BM

• Usually a single tear involving the lesser curve below GEJ (50-80%) • Co-existent with other sources of UGI in 30-80% patients • Resolves without surgery 90% – Endoscopy, angiography • Surgery: High gastrotomy, oversewing – Check for other UGI bleeding points*

• Case: 80 yo woman wih chronic microcytic anemia presents to the ED with acute-onset chest pain. Cardiac workup is negative. She is retching but there is no emesis. CXR demonstrates a large gastric air bubble behind the heart and free air under the diaphragm.

• Diagnosis?

• Management?

Gastric volvulus

• Present with abdominal pain, distention, UGIB, vomiting, retching • Acute volvulus is an emergency • Reduce volvulus, repair hiatal defect, gastropexy or tube fixation