Small bowel adenocarcinoma - DBaril

Small bowel adenocarcinoma - DBaril - Small bowel...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Small bowel adenocarcinoma Small Tumor Board Englewood Hospital and Medical Center Donald Baril Department of Surgery Mount Sinai School of Medicine December 10, 2004 Case presentation – R.H. Case 79 yo F presented with progressive fatigue and 79 shortness of breath shortness PMHx: Esophageal cancer, papillary bladder cancer, PMHx: endocarditis, hypertension, atrial fibrillation, CAD, hypothyroidism, CVA hypothyroidism, PSurgHx: Esophagogastrectomy/Splenectomy (6/03), PSurgHx: CABG/MVR (5/03) CABG/MVR Case presentation – R.H. Case Found to be markedly anemic with a hematocrit of 18 October 2004 – negative endoscopy and colonoscopy; October capsule endoscopy showed two small bowel ulcers capsule CT scan – lumen constricting lesion of mid-small CT bowel bowel Planned exploratory laparoscopy in mid-November November 2004 – right hemispheric stroke Case presentation – R.H. Case November 23 – Exploratory laparoscopy converted to November open lysis of adhesions, small bowel resection open Returned emergently to the OR immediately postoperatively for intraabdominal bleeding Case presentation – R.H.: Pathology Case Moderately differentiated invasive adenocarcinoma Moderately with focal adenosquamous features and minor mucinous component mucinous Transmural invasion Lymphovascular invasion Lymph node metastasis (1/7 lymph nodes) Epidemiology of small bowel adenocarcinoma Epidemiology Small intestine accounts for approximately 75% of the Small length of the GI tract and more than 90% of the mucosal surface surface Fewer than 2% of GI malignancies arise in the small Fewer intestine intestine Incidence of small bowel malignancies is 1 per 100,000 Estimated to be less than 5000 cases per year diagnosed Estimated in the U.S. in Small bowel tumors Small Small bowel malignancies Small 30-50% are adenocarcinomas 25-30% are carcinoids 15-20% are lymphomas 10-20% are gastrointestinal stromal tumors Anti-neoplastic environment of the small intestine Anti-neoplastic 1. 2. 3. 4. 5. 5. Liquid contents cause less irritation than more solid Liquid contents of large bowel contents Rapid transit of intestinal contents provides shorter Rapid exposure of mucosa to carcinogens exposure Lower bacterial load may result in decreased Lower conversion of bile acids into potential carcinogens conversion Benzopyrene hydroxylase, enzyme responsible for the Benzopyrene conversion of the known carcinogen benzopyrene, is present in higher concentrations in the small bowel Increased lymphoid tissue and higher levels of IgA Clinical presentation Clinical Abdominal pain Nausea and vomiting Bleeding/Anemia Weight loss Gastric outlet obstruction Diarrhea Mean time to diagnosis from the onset of the initial Mean complaint is 7 months complaint 50% of patients present emergently with 50% obstruction or bleeding obstruction Diagnosis of small bowel malignancies Diagnosis Plain abdominal radiographs Obstruction Calcified mass UGI/SBFT Mass Mass Mucosal defect Intussusception Diagnosis of small bowel malignancies Diagnosis Enteroclysis NGT directed to the jejunum and a combination of NGT barium and methylcellulose is instilled barium Reported sensitivity of 90% Reported for detecting small bowel tumors vs. 50% for SBFT tumors Diagnosis of small bowel malignancies Diagnosis CT Study of choice for preoperative staging and evaluation of Study metastases metastases CT enteroclysis MRI Ultrasound Diagnosis of small bowel malignancies Diagnosis Endoscopy/Enteroscopy Push enteroscopy allows for visualization of 40-60 Push cm of small bowel beyond the ligament of Treitz cm Intraoperative endoscopy EUS Useful in the evaluation of ampullary tumors Diagnosis of small bowel malignancies Diagnosis Capsule endosocopy Diagnosis of small bowel malignancies Diagnosis Exploratory laparotomy/laparoscopy Most sensitive diagnostic modality Preoperative diagnosis of small bowel malignancy Preoperative is made in only 50% of cases is Should be considered for all cases in patients with Should occult GI bleeding, weight loss, unexplained abdominal pain abdominal Clinical features of small bowel adenocarcinoma Clinical Majority arise in the duodenum and jejunum Increased exposure to pancreatic and biliary Increased secretions secretions Exception is in patients with Crohn’s, in whom the Exception most common site is the terminal ileum most Peak incidence is in the 7th decade Male: Female ratio of 2.4:1 Risk factors for small bowel adenocarcinoma Risk Pre-existing adenoma, either single or multiple Pre-existing 300-fold increased risk in patients with FAP Crohn’s Crohn’s Celiac disease Celiac IgA deficiency Alcohol abuse Neurofibromatosis Urinary diversion procedures ? Red meat Crohn’s disease and adenocarcinoma Crohn’s 12-fold increased risk of small bowel cancer Symptoms often mimic symptoms of Crohn’s Risk factors Long duration of disease Male gender Fistulas Surgically excluded loops of small bowel Strictures Immunosuppressive drugs Staging of adenocarcinoma of the small intestine Staging Stage I – tumor confined to the lamina propria, submucosa, or Stage muscularis propria muscularis Stage II – tumor extending beyond the muscularis propria or Stage invading adjacent structures invading Stage III – tumors with any bowel wall extension and positive Stage lymph nodes lymph Stage IV – tumor with any degree of bowel wall invasion, Stage with or without lymph node metastases, and with distant disease disease Adenocarcinoma of the small intestine Adenocarcinoma Study Location Stage at presentation Duodenum Duodenum and jejunum and Cunningham et Cunningham al. Annals of Surgery Annals 1997 Talamonti et Talamonti al. al. Archives of Archives Surgery Surgery 2002 Ileum I II III IV 79% 21% 6.9% 24% 24% 45% 76% 24% 4.8% 19% 38% 38% Adenocarcinoma and therapy Adenocarcinoma Surgery is the treatment of choice Surgery Procedure of choice is determined by location of tumor: 1st and 2nd portion of the duodenum – pancreaticoduodenectomy Distal duodenum – resection and duodenojejunostomy Jejunum and ileum – segmental resection including Jejunum wide mesentery resection (6 inches) wide Terminal ileum – right hemicolectomy Surgical pearls Surgical Resection of adequate mesentery is often limited by Resection proximity of nodes or tumor to the SMA proximity Margin-status must be confirmed by frozen-section if Margin-status in question in Patients with metastatic disease should undergo Patients resection in most cases to prevent later complications resection Adjuvant therapy Adjuvant Patients who undergo radical surgery often later die Patients from distant disease recurrence from No proven survival benefit No prospective studies 5-fluorouracil has shown the most promise Adenocarcinoma of the small bowel Adenocarcinoma Dabaja SD et al. Cancer June 2004 Dabaja June Survival Survival Overall 5-year survival of 26% Median survival time of 20 months Aggressive treatment and increased survival Aggressive Prognosis Prognosis Overall 5-year survival of 30% Overall 40-60% for resected tumors 15-30% for non-resected tumors Stage I – 100% Stage II – 52% Stage III – 45% Stage IV – 0% Prognosis Prognosis Study Cunningham et Cunningham al. al. Annals of Surgery Annals 1997 Curative Curative resection rate rate Overall 5 Overall year year survival survival 66% 62% Median survival time Median (months) Noncurative Noncurative resection resection Curative Curative resection resection 30% 7 23 37% 9 40 Talamonti et al. Archives of Surgery 2002 Prognosis Prognosis Poor prognosis correlated with: Mural penetration Nodal involvement Distant metastasis Perineural involvement Large tumor size Poor histologic grade Metastatic disease involving small bowel Secondary neoplastic involvement of small intestine Secondary is more frequent than primary small bowel neoplasia is Primary tumors of the colon, ovary, uterus, and Primary stomach typically involve the colon by direct stomach invasion or intraperitoneal spread invasion Primary tumors from breast, lung, and melanoma Primary breast, metastasize to small bowel hematogenously metastasize Metastatic disease involving small bowel Metastatic Treatment is palliative Limited resection Limited Intestinal bypass Melanoma Metastatic focus may further disseminate to small Metastatic bowel mesentery and draining lymph nodes bowel Aggressive resection may improve disease-free Aggressive survival survival Esophageal cancer and metastases Esophageal Patients with esophageal cancer usually present with Patients recurrence within 2 years recurrence Treatment of solitary metastasis appropriate when: Contained with a single organ that can be easily resected Good overall patient function No local recurrence of primary tumor > 1 year after the initial treatment Gastrointestinal stromal tumors Gastrointestinal Visceral sarcomas, previously classified as Visceral leiyomyomas and leiyomyosarcomas leiyomyomas Now classified as GISTs with a range of biological Now behaviors from low grade to high grade malignancies behaviors Traditionally, microscopic findings were used to Traditionally, define malignancy including: define Increased cell size Increased cell irregularity Lack of cell differentiation Presence of cells with hyperchromic and multiple nuclei GISTs – Tumor biology GISTs Proposed to arise from the interstitial cell of Cajal, an Proposed interstitial an intestinal pacemaker cell of mesodermal origin intestinal Similar cell markers to those of normal Cajal cells 1) myeloid stem cell antigen CD34 2) KIT receptor tyrosine kinase 3) variably positive for smooth-muscle actin 4) usually negative for desmin Previously thought to be smooth muscle neoplasms but now Previously accepted to have: accepted 1) myogenic features (smooth muscle GIST) 2) neural features (GI autonomic nerve tumor) 3) myogenic and neural features (mixed GIST) Clinical features of GISTs Clinical Most commonly present with pain and weight loss Most commonly present in the 6th and 7th decades but may occur at any age may Distribution of occurrence is proportional to the Distribution length of the segments of the small bowel Lesions occur in extraluminal, subserosal locations Often develop central ischemia and necrosis that Often leads to bleeding leads GISTs of the small intestine GISTs Study Location Stage at presentation Duodenum Duodenum and jejunum and Cunningham et Cunningham al. Annals of Surgery Annals 1997 Ileum I II III IV 75% 25% 25% 12.5% 0% 63.5% 80% 20% 12% 20% 48% 20% Talamonti et al. Archives of Surgery 2002 GISTs of the small intestine GISTs Study Cunningham et Cunningham al. al. Annals of Surgery Annals 1997 Curative Curative resection rate rate Overall 5 Overall year year survival survival 50% 84% Median survival time Median (months) Noncurative Noncurative resection resection Curative Curative resection resection 25% 9 66 22% 22 66 Talamonti et al. Archives of Surgery 2002 Prognostic factors and therapy of GISTs Prognostic Only complete resection has been found to be a Only significant favorable prognostic factor significant Surgical resection is therefore the mainstay of therapy Surgical and should include any involved adjacent organs and Complete resection results in 3 and 5-year survival rates of 54% and Complete 42% compared to 13% and 9% after incomplete resection 42% No added benefit to wide resections or extensive No lymphadenectomies lymphadenectomies Prognostic factors and therapy of GISTs Prognostic Poor prognostic factors include tumors greater than 5 Poor cm, non-smooth muscle cell differentiation, and those classified as high grade classified Metastases present in 30%; most commonly hepatic Recurrence rates of 25-50% reported No demonstrable benefit of adjuvant therapy GISTs and STI-571 – Molecular therapeutic options GISTs Most GISTs (52-85%) have a gain-of-function Most mutation in the c-kit proto-oncogene mutation Results in ligand-independent activation of the KIT Results receptor tyrosine kinase Unopposed stimulus for cell growth STI-571 STI-571 molecule which inhibits: Enzymatic activity of the KIT tyrosine kinases, Platelet-derived growth factor receptor Platelet-derived BCR-ABL fusion protein GISTs and STI-571 – Molecular therapeutic options GISTs Initial phase II trial of STI-571 in patients with metastatic Initial GISTs (follow-up of three months) GISTs Partial response rate in 59% Stable disease in 27% Progression of disease in 13% 86% had a mutation in c-kit and were more likely to respond EORTC study showed similar results Partial response rate in 69% Stable disease in 19% Progression of disease in 11% Dematteo et al. Human Pathology. May 2002 Human Carcinoid Tumors of the Small Intestine Originally described by Oberndorfer in 1907 Arise from Kulchitsky cells Type of enterochromaffin cell Cells of the amine precursor uptake decarboxylase Cells (APUD) system which have the ability to synthesize biologically active substances biologically Clinical features of carcinoid tumors Clinical Most commonly present in the 7th decade Often present with nonspecific complaints Up to 50% of patients present with obstruction Carcinoid syndrome, marked by flushing and diarrhea, is rare Carcinoid and occurs in only 5-7% of patients and Right sided valvular fibrosis occurs late in the disease Right Increasing frequency from the duodenum to the ileum Pathological features of carcinoid tumors Pathological Carcinoid invasion into the mesentery leads to Carcinoid fibrosis and often kinking of the small intestine fibrosis Thickening of the vessel wall is also present and may Thickening lead to ischemic changes in the gut lead Serotonin is postulated to be responsible for these Serotonin features features Diagnosis of Carcinoid Tumors Diagnosis Traditional studies may fail to demonstrate the Traditional primary tumor primary Indium-labeled octreotide scan is the most accurate Indium-labeled (sensitivity of 90%) means of localizing a carcinoid tumor tumor Tumor cells express somatostatin receptors which take up Tumor octreotide octreotide 24-hour urine levels of 5-hydroxyindoleacetic acid 24-hour (5-HIAA) may alone be diagnostic (5-HIAA) Serotonin is metabolized in the liver to 5-HIAA and Serotonin excreted in the urine excreted Carcinoid tumors of the small intestine Carcinoid Study Location Stage at presentation Duodenum Duodenum and jejunum and Cunningham et Cunningham al. Annals of Surgery Annals 1997 Ileum I II III IV 28% 72% 11% 0% 22% 66% 22% 78% 8% 24% 38% 30% Talamonti et al. Archives of Surgery 2002 Carcinoid tumors of the small intestine Carcinoid Study Cunningham et Cunningham al. al. Annals of Surgery Annals 1997 Curative Curative resection rate rate Overall 5 Overall year year survival survival 67% 65% Median survival time Median (months) Noncurative Noncurative resection resection Curative Curative resection resection Not Not reported reported 18 81 64% 32 Not Not reached reached Talamonti et al. Archives of Surgery 2002 Surgical therapy of carcinoid tumors Surgical excision is the mainstay of therapy Isolated disease is widely resected Synchronous tumors are found in 33-40% of patients Synchronous and should all be excised if feasible and Noncarcinoid synchronous tumors are found in up to Noncarcinoid 25% of patients 25% Typically tumors of the breast, lung, stomach, or colon Surgical therapy of carcinoid tumors Surgical Tumor size is an unreliable predictor of metastatic Tumor disease disease Aggressive attempts should be made to resect Aggressive metastatic disease Decreases the need for medical therapy Prolongs survival Hepatic metastases Surgical resection Hepatic artery embolization Cryosugery Radiofrequency ablation Transplantation Medical therapy of small bowel carcinoid tumors Octreotide inhibits tumor secretion of hormones Octreotide May have a direct tumor control effect on carcinoid tumors Relieves flushing in 76% of patients Relieves Improves diarrhea in 83% Decreases the urinary 5-HIAA levels in 80% Interferes with endo-and exocrine pancreas function Medical therapy of small bowel carcinoid tumors Medical Interferon-alpha has shown improvement in Interferon-alpha symptoms in 68% and a biochemical response in 42% symptoms Response to chemotherapy has been variable and Response short lived short Use limited by high incidence of side effects Combination of streptozocin and 5-fluorouracil has shown Combination a 20-30% response rate 20-30% No proven benefit of radiotherapy Conclusions Conclusions Small bowel malignancies although rare are associated with Small relatively poor 5-year survival rates relatively Abdominal pain of unknown origin should prompt a limited Abdominal investigation for these tumors investigation Surgical therapy remains the mainstay of therapy Surgical Future directions in the therapy of these tumors include the Future use of direct molecular modification and immunotherapy use ...
View Full Document

This note was uploaded on 12/21/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

Ask a homework question - tutors are online