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 increase acid• Cholecystokinin - duo GB contraction, pancreatic

secretion• Secretin – duo S cells bicarb release, pancreatic

secretion• Glucagon – panc α cells increase gluc release • VIP – gut SM relaxation, increase gut secretion• Gastric inhibitory peptide = glucose insulinotropic peptide –

K cells of gut induce insulin secretion• Somatostatin – gut global gut inhibition• Motilin – Mo cell of SB upregulate MMC• Peptide YY – gut global inhibition• Neurotensin – SB 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

• 2nd/3rd 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

• 10th most common malignancy in US– More common in males, African-Americans,

Hispanics, Native Americans

• 2nd 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