ONCOLOGIA DIGESTIV~

NOIEMBRIE 2014

1. EVENIMENTE PRECOCECiclul celular :

G0 faza de repaosG1 preg`tirea sintezei ADNS sinteza ADN - celule tetraploideG2 pauz` M mitoz`

Pierderea controlului prolifer`rii:

- proliferare [n cripte (strat bazal malpighian)

- alungirea genei APC beta catenina rol [n reglarea cromozomilor

2. EVENIMENTE INTERMEDIARE Expansiunea clonal`

Ki rasp 53 Transformarea malign`- pierderea cromozomial` (LOH)- instabilitatea microsateli\ilor (MSI=RER)

3. EVENIMENTE TARDIVEInstabilitate genetic`

Pierdere de proteine esen\iale

Evenimente genetice virulente

Anume clone - metastazeaz`

DATE GENETICECancerul colorectal va servi drept model din ra\iuni de:

- inciden\` (13-14%)- ad@ncirea cercet`rilor- rezultate palpabile

1985 . Biologia molecular` a demonstrat :- pierderi alelice bra\ scurt C17bra\ lung C5bra\ lung C18- activarea Ki rasN ras- deosebiri colon drept/st@ng

CARCINOGENEZA DIFERIT~1. Argumente embriologicea) origine diferit`b) surse vasculare deosebite2. Argumente histologicea) bog`\ia de celule endocrine

3. Argumente biochimice:A) bog`\ia ornitindecarboxilazei [n colonul ]i cancerul st@ng.B) metabolizarea acetat/butiratC) metabolizarea dimetilhidrazidei

4. Argumente epidemiologice:

a) inciden\` diferit`b) sc`derea riscului la femeile multiparec) colecistectomia influen\eaz` inciden\a cancerului proximal

5. Date genetice:Existen\a a dou` tipuri de cancer ereditar:Forme polipoase polipoza familial` colonic` (A.P.C):- S. Gardner- S. TurcotForme nonpolipoase - Lynch I - Lynch II Azi= A- LOH + B- MSI

Caractere cancere LOH+

20 % cromozomi cu dele\ii alelice intereseaz`: C17 p 53 C18 DCC, SMAD C5 A.P.C. ; MCC C22 C8

au prognostic mai prost

intereseaz` 80% cancere colorectale

2/3 tumori pe colonul st@ng

Caractere cancere MSI Euploidie Cromozomi C2, C3, C7 Intereseaz` Colonul drept Prognostic mai bun De]i - sunt multiple - sincrone - sunt nediferen\iate

Protooncogene

Ki-ras C11N-ras C1H-ras C12

Se g`sesc [n egal` m`sur` ]i [n cancereaneuploide (LOH) si euploide (MSI).

ST~RI PRECANCEROASEPolipii adenomato]i:Secven\a AdenomCarcinom e indubitabil`:1.Epidemiologic - distribu\ie similar` - v@rsta difer` cu 3-5 ani2.Distribu\ie anatomic` identic`3.Date histopatologice4.Date experimentale5.Date de profilaxie primar`

Sindroame polipoase (Genetice)

TipPattern transmisieCromozomGen`FAP + GARDNERA.D5APC > 5qAFAPA.D5APC < 5qTURCOTA.D5,(2,3,7)APC HNPCCHNPCCA.D237MSH2 PMS1MLH1PMS2Polipoza juvenil`A.DhamartoameProtein-tirozinfosfatPeutz JeghersA.D19Treoninkinaza

SINDROAME GENETICE RARE

C 1ORuvacalba-SmithHamartoameLipoameHemangioameLimfangioameCowdenHamartoame gastrice si co loniceC 10 SMAD4Polipoza familiala juveni laHamartoame

GENACROMOZOMFUNCTIANORMALAMANIF.CLI NICEAPC 5qRegleaza apoptozaAdenoameK rasvariatiTraduc raspuns mitogenicMutanta 50%p53C17pRegleaza ciclul celularCheie in malignizareDCCC18qSupresoarePromoveaza progresiaMMRvariatiExcizia bazelor eronate

Levine J and Ahnen D. N Engl J Med 2006;355:2551-2557U.S. Consensus Guidelines for Colonoscopic Surveillance after Polypectomy

*Table 1. U.S. Consensus Guidelines for Colonoscopic Surveillance after Polypectomy.

Ace]ti polipi se pot [nl`n\ui [n tot lungul tubului digestiv.Malignizarea dependent` de:1. Talie2. Num`r3. Tip4. Displazie

Criteriile Amsterdam II

3 pacien\i2 genera\iiLeg`tur` gr IDebut < 50 aniMSI

Adenom PolipAdenoame Plate MUTO (1985) 10-40%Adenoame Din\ate KUDO (1996) I. Rotunde II. Ovale III. S>L tubulare , rotunde IV. Ramificate V. Nonstructurale

Cromoendoscopie + magnificare

ALTE ST~RI PRECANCEROASE

A. Colon

Boli inflamatorii nespecifice

Apendicectomia

Ureterosigmoidostomia

B. Stomac

Ulcer gastricGastrite cronice atroficeAnemia BiermerStomacul operat

C. Esofag Stenoze benigne Achalazia S. Plumer Vinson S. Torre Muir - acantoame S. Howell Evans keratodermie B. celiac`

Factori exogeni infec\io]iPapiloma virus esofagHelicobacter pylori stomacColon - APC

/Beta catenin` /H.P. > gastrina > polip.Ficat virusurile B, C

Factori alimentari Anume constituen\i sunt nocivi:AlcoolFumat

Dar mai ales lipsa de protectori ]i nu excesul de factori nocivi

Alimenta\ia ]i preven\ia cancerelor digestive

Evitarea supraponderalit`\iiAlimenta\ie bogat` [n vegetaleCereale completeMicronutrien\i - seleniu - vitamine antioxidante (A, E, C)

Diagnosticul cancerelor precoce DEFINI|IE: Cancerul precoce intereseaz` mucoasa sau/]i submucoasa indiferent de existen\a metastazelor la distan\`.

Clasificarea Societ`\ii Japoneze de Endoscopie Digestiv` (1963)

Cancer in situ:- nu dep`]e]te membrana bazal`- termen pe cale de abandonare

Cancer precoce (mai bine spus superficial)Tip protruzivSuperficiala) supradenivelatb) planc) subdenivelatUlcerat

Cancer avansat (Borman)PolipoidUlceratUlceroinfiltrantInfiltrant:

a) skirb) linit` plastic`

Clasificarea Paris 2002Tip 0 superficialTip 1 cancer polipoidTip 2 cancer ulcerat bine demarcatTip 3 ulcerat,infiltrativ, prost delimitatTip 4 infiltrativ difuzTip 5 neclasificabil

Clasificarea VienaNegativ IENNedefinit IENGrad redus IENadenom/displazieGrad inalt displazie (intraepitelial sau intramucozal)adenom cu displaziecancer neinvazivb`nuial` de cancer invazivcancer intramucozal(lamina propria)Cancer submucos

Diagnosticul de cancer precoce impune:

Demonstrarea malignit`\iiStabilirea gradului de penetrare

Demonstrarea malignit`\iiDeocamdat` este apanajul examenului HISTOPATOLOGIC.De unde se preleveaz` biopsii:Zone suspecte:Supradenivelate palidePlate eritroplaziceRigide

Citologia abraziv`

{nt`rirea ]i localizarea leziunii:CROMOENDOSCOPIA:Esofag:

Lugol 1-2,5%Albastru de toluidin` 1% pentru carcinomul epidermoidAlbastru de metilen 0,5% pentru metaplazia intestinal`Echoendoscopie

2. Colon (clasificarea KUDO)Pit rotund / inflamatorpolip Pit ovalar / hiperplazicPit tubular L adenom

S Pit ramificat -> adenom degeneratPit nonstructural cancer interes@nd submucoasa

Epiteliu normalEpiteliu hiperproliferativAdenom precoceC2KrasCOX2C17 P53Adenom intermediarAdenom t@rziuCancerC18DCCFAP;5gC8Metastaze

Tratamentul cancerului incipientMucosectomia:Limite generale tip/m`rimeInjectare 20 ml serLimiteaz` riscul perfora\ieiFace leziunea polipoid`Marturise]te lipsa de invazieLimitare cu electrocauterul0,4% hemoragii0,7% perfora\ii

Distrugere:Laser Nd YAG 97 % succes

1064 nm 7-14% complica\iiFotodinamic hematoporfinie

ac 5 ALA - rosu 630nm80% succesAPC

Cum se face diagnosticul de cancer precoce ?

Simptomatici esofag

Supravegherea st`rilor preneoplazice

Programe de depistare activ`

Tratamentul cancerelor avansate Chirurgie - curativ`

- paleativ`Radioterapie - neoadjuvant`

- singur`Chimoterapie - idem

Medicamente1. 5 FU -> blocheaz` TS ADN (continuu) / ARN (frac\ionat)2. Capecitabina -> blocheaz` pirimidinnucleozidfosforilaza (FTORAFUR = URACIL+TEGAFUR)3.Deriva\i platin` - cisplatin - oxaliplatin4.Camptotecin inhibitor topoizomeraza5.Avastin anti VEGF

Medicamente (2)Doxorubicin`Bleomicin`Mitomycin` CRalitrexed inhibitor TSTaxoter

CANCERUL DE ESOFAG

Epidemiologie

Raport sexe 3/1 (20/1 Bretania, 1/1 China)V@rsta: 70-80 aniPrevalen\a: - 7 la 100 000 SUA - 130 la 100 000 ChinaRasa negrii x 4 albi SUA

EtiologieTyloza autosomal dominant

- S. Howell-Evans - tulb. Vitamina AS. Torre-MuirB. Celiac`Agregare familial`

Alcoolul Acetaldehid` Nitrozamine Uretani Tanin Micotoxine Pesticide ViPe l@ng` - [ncetinirea ciclului celular - reducerea sintezei ADN - inhib` repararea lui

Fumatul

Nitroso: - nornicotina - noranabazina - noranatabina

Nu poten\eaz` efectul alcoolului

Alimente

Vit A (retinol, carotenoizi) Vit E Mo (cofactor al nitratreductazei) Vit C Ac elagic Se (reduce peroxizii)

Alte CauzePapilomavirusulRadia\iiImunosupresiveProfesii vulcanizatori

Leziuni precanceroase

Esofagit` BarrettS. Plummer-VinsonAchalaziaEsofagita caustic`Alte cancere ORL

Spechler S. N Engl J Med 2002;346:836-842The Use of Endoscopic Landmarks to Distinguish Normal Esophagus (Panel A) from Barrett's Esophagus (Panel B)

*Figure 2. The Use of Endoscopic Landmarks to Distinguish Normal Esophagus (Panel A) from Barrett's Esophagus (Panel B).

The squamocolumnar junction, or Z line, is the visible line formed by the juxtaposition of squamous and columnar epithelia. The gastroesophageal junction is the imaginary line at which the esophagus ends and the stomach begins. The gastroesophageal junction is identified endoscopically as the most proximal part of the gastric folds. In normal esophagus, the squamocolumnar junction and gastroesophageal junction often coincide, and there is no columnar epithelium between the two (Panel A). The inset in Panel A shows normal stratified squamous epithelium. In Barrett's esophagus, the squamocolumnar junction is proximal to the gastroesophageal junction (Panel B). The area between the two junctions consists of columnar epithelium with specialized intestinal metaplasia (inset in Panel B). Modified from Spechler4 with the permission of the publisher. (Inset in Panel A, hematoxylin and eosin, x80; inset in Panel B, hematoxylin and eosin, x100.) Photomicrographs provided by Dr. Edward Lee.

Spechler S. N Engl J Med 2002;346:836-842Endoscopic Photograph Showing Traditional, or Long-Segment, Barrett's Esophagus

*Figure 1. Endoscopic Photograph Showing Traditional, or Long-Segment, Barrett's Esophagus.

Reddish, columnar epithelium extends more than 3 cm above the gastroesophageal junction.

Enzinger P and Mayer R. N Engl J Med 2003;349:2241-2252Endoscopic Image (Panel A) and Endoscopic Ultrasonogram (Panel B) Showing a Transmural Adenocarcinoma of the Esophagus Associated with Barrett's Esophagus (Short Arrows), with Lymph-Node Metastases (Long Arrow)

*Figure 2. Endoscopic Image (Panel A) and Endoscopic Ultrasonogram (Panel B) Showing a Transmural Adenocarcinoma of the Esophagus Associated with Barrett's Esophagus (Short Arrows), with Lymph-Node Metastases (Long Arrow).

Courtesy of John Saltzman, M.D.

Factori de risc pentru cancerul esofagian

Factorul de riscCancer scuamosAdenocarcinom1.Fumatul+ + ++ +2. Alcoolul + + +-3. Esofagul Barrett -+ + + +4.Simptome de reflux-+ + + 5.Obezitatea -+ +6.S`r`cia + +-7.Leziuni caustice+ + + +-8.S. Plummer-Vinson+ + + +-9.Alte cancere ORL+ + + +-11.Rx terapie+ + ++ + +12.B`uturi fierbinti+13.Utilizarea blocante+/-

Anatomie patologic`Macro: 1. Proliferativ2. Ulcerativ3. StenozantMicro:1. Carcinom epidermoid2. Adenocarcinom3. Alte epiteliale/nonepiteliale

Evolu\ie

Local`:

a) incipientb) avansatRegional` aorta/TR BRLa distan\` sanguin/limfatic

Simptome cancer precoce

Durere [n punct fixSenza\ie la trecerea boluluiDisfagie paradoxal`Algie jugulo-carotidian`Parestezii faringiene

Cancer avansatObstruc\ie:a) disfagie 75%b) regurgita\iic) sl`bire 60% (reducere BMI cu peste 10% - prognostic prost)Invazie local`:a) modificarea vociib) dureri retrosternalec) s. brono pulmonare dispnee, tused) dureri epigastriceSemne la distant`a) adenopatieb) hepatomegaliec) revarsat pleural

Diagnostic Metode imagisticeAfirmarea cancerului

1. Endoscopie2. Cromoendoscopie3. Radiologie 4. Anatomie patologic`Evaluarea extensiei

1. Echoendoscopia2. CT.3. PET 18 fluordezoxiglucoza4. Toracopscopie 5. Laparoscopie

Tratament curativ Cancer precoce Cancer avansat

Mortalitateaperioperatorie 2,5% 30%

La 5 ani 15 % 80-90%

La 10 ani 90%

PET.

Tumorile g-I au glicoliza crescuta, deci tranzit crescut de glucoza.

18 F deoxiglucoza>radio trasor ce emite POZITRONI

MECANISM

18 F DEOXIGLUCOZA SUB ACTIUNEA UNEI HEXOKINAZE GENEREAZA FDG-6 PO4 CARE SE STOCHEAZA INTRACELULAR

Imagistica Cuplarea cu tomografia computerizata furnizeaza date :

metabolice anatomice

Conditii de examinare

Pacient a jeun

Echilibrat glucidic

Departe de terapie

Durata 20-60 min

IndicatiiUrmarire dupa rezectii

Recidiva pelvina

Metastaze ganglionare

Metastaze peritoneale

Terapii endoscopice

Mucosectomia

Electrorezec\ia bipolar`

Distruc\ia fotodinamic`

Paleative

Dilata\ia

Distruc\ie cu laser

Protezare

Dam J and Brugge W. N Engl J Med 1999;341:1738-1748Endoscopic Laser Therapy

*Figure 5. Endoscopic Laser Therapy. Panel A shows the endoscopic appearance of the gastroesophageal junction in a patient with an adenocarcinoma causing near-total obstruction. The patient declined chemoradiation therapy and was not deemed a candidate for surgery, because of severe coexisting illness. In Panel B, the same area is shown after endoscopic laser photoablation of the tumor. Luminal patency had been restored. A hiatal hernia can be seen beyond the treated tumor.

CANCERUL GASTRIC

Cancerul gastricEpidemiologie

Prevalen\` (0/suta de mii de loc./an)- 120-140 Japonia - 60 Germania- 8-20 SUA

Raport Sexe 3/1

Rasa: - Japonezii - Negrii

EtiologieHelicobacter Pylori

- maltom- tip intestinalFactori genetici

- gena p53- agregare familiar`- grupa de s@nge A

St`ri precanceroase

Gastrita atrofic`Anemia BiermerPolipii gastriciUlcer gastricStomacul rezecat

Alte st`ri

Schwannoame 10 20%

Leiomioame 10% (stromale)

Neurofibroame

Anatomie patologic`Carcinoame

a) simpleb) ADK mucoid/nesecretantc) mucipard) adenoacantoameSarcoame

a) limfoame Maltomb) fibroc) leiod) angio

MacroscopicCancer Precoce:ProtruzivSuperficial

a) suprab) platc) subUlcerat

Cancer Avansat-BormannProliferativ polipoid exofilicUlceratUlceroinfiltrantInfiltrant:- SKIR glande- L.P. trabecular

PrognosticSupravie\uire la 5 ani:

93% M85% SM40% MP15% S

SimptomatologieModific`ri de apetitSindrom cardialSindrom piloricSindrom ulcerosHDSDiaree

Manifest`ri paraneoplaziceAnemie hemolitic`

Acantosis nigricans

Dermatomiozita

Hipergastrinemie

Acanthosis NigricansFargnoli MC, Frascione P. N Engl J Med 2005;353:2797-2797.

*A 37-year-old man was evaluated because of a two-year history of asymptomatic thickening and darkening of the skin on his axillae (Panel A), neck, face, and arms. The patient had no history of diabetes mellitus or other endocrine disorders, alcohol abuse, or chronic hepatitis. On examination of the skin, brown patches and plaques with elevated ridges and a velvety feel were observed on the axillary regions, the neck, the antecubital fossae, the dorsal aspect of the hands, and the malar and periorbital regions. Cutaneous findings were consistent with the diagnosis of acanthosis nigricans. An evaluation for cancer revealed a hepatic mass, 20 by 17 cm. The patient underwent right hepatic lobar resection. Histopathological examination of the resected tissue showed a moderately differentiated hepatocellular carcinoma with extensive hemorrhagic, necrotic, and sclerotic areas (T2N0M0). Three months after surgery, a spontaneous complete regression of cutaneous lesions occurred (Panel B). Malignant acanthosis nigricans is a rare form of acanthosis nigricans that precedes or occurs in association with often aggressive internal cancers and usually correlates with the evolution of the underlying neoplasm.

ClinicaPalparea tumorii

Metastaze:- ggl. Troisier- ombilic- fund de sac- hepatomegalie

Virchow's NodeSiosaki MD, Souza AT. N Engl J Med 2013;368:e7.

*A 64-year-old man presented with a 6-month history of epigastric pain, weight loss, and nausea. In the previous 3 months, he had lost 10 kg. On examination, he was noted to have a nontender, firm, fixed, left supraclavicular lymph node measuring 3.0 by 2.5 cm. Upper endoscopy revealed an adenocarcinoma of the gastric corpus. Computed tomography of the abdomen showed liver metastasis. Virchow's node, or Troisier's node, refers to carcinomatous involvement of the supraclavicular nodes at the junction of the thoracic duct and the left subclavian vein. Usually, nodal enlargement is caused by metastatic gastric carcinoma, although supraclavicular nodal involvement can also be seen in other gastrointestinal, thoracic, and pelvic cancers. Gastric cancers tend to metastasize to this region by means of migration of tumor emboli through the thoracic duct, where subdiaphragmatic lymphatic drainage enters the venous circulation in the left subclavian vein. Given the patient's low performance status, according to his Karnofsky performance-status score and his score on the Eastern Cooperative Oncology Group Performance Status scale, chemotherapy was contraindicated, and he was referred for palliative radiotherapy.

DiagnosticAsimptomatici

- antecedente ereditare- polipi- a Biermer- ocazionalSimptomatici

- dispensarizare

Diagnosticul Cancerului AvansatImagistic

Diagnosticul diferen\ialUlcer gastric benignCiclul benign/malignAlte tumori

Tricobezoar

Evolu\ie

Extensie direct`Limfatic embolie/permea\ieVascular embolieTransplantare

TratamentCURATIV

CHIRURGICAL

ENDOSCOPIC

Paleativ

Impus de complica\ii Endoscopic Chimioterapie

LimfoameLocalizarea digestiv`: 12,5%

Reprezint`: - 3% T. maligne stomac - 12-18% T. maligne intestin - 1% T. maligne colo-rectale

EtiologieDeficite imune - legate de sex lgM

- Wiskott-AldrichHIVImunodeprima\iB. celiac`, dermatita herpetiform`H. pylori , Heilemani

Clasificarea Ann Arbor

I E 1-n segmenteII 1E 1-n segmenteII 2E 1-n + ganglioni dep`rta\iIII E 1-n + ganglioni supradiafragmaticiIV E 1-n + alte viscere

Clasificare IsaacsonFenotip B: - MALT grad jos/grad [nalt

- limfom mediteranean - limfom al mantalei - limfom Burkitt

Fenotip T cu/f`r` enteropatie asociat`

Conceptul modernMALT 4 componenteP. PeyerLamina propriaLimfocite T intraepitelialeGanglioni mezentericiLNH - sunt malignit`\i MALT:Normal intestin , colonDob@ndit dup` infec\ia HP

Limfom al zonei marginale (joas` malignitate CD5-CD10Limfom B cu celule mariLimfom cu celule din manta (polipoza limfatomoas`)Limfom folicularLimfom Burkitt

Limfom al zonei marginale MALT (malignitate )

Infiltrat al corionuluiHiperplazie limfoid`Leziuni limfoepitelialeEvolu\ie lent`, localizat`

Limfomul mantalei Polipoza limfoid`

Intereseaz`:

- intestinul, colonul- ganglionii mezentericiPoate fi:

- primitiv- st IV

Limfomul folicular:p`streaz` caracterele limfomului ganglionar echivalent.

Limfomul Burkitt:localizarea ileo-cecal`

Limfomul B cu celule mari:cel mai frecventforma ulcerativ`/obstructiv`

Diagnostic pozitivSimptome nespecificeHistologicEndoscopic :- ulcera\ii- pliuri [ngro]ate- stenoz`- polipoz`

Bilan\ul extensieiEx. Clinic: - semne generale

- ggl, ficat, splinaBiologic: - hemoglobina, CA, P, ac. Uric

- 2 microglobulina - markeri limfocitariTub digestiv: - endoscopie

- echoendoscopieAlte:- CT

- Rx pulmon- ECG

TRATAMENT

Limfom marginal

DiagnosticTratament: 7 zile, triterapie Control 6 s`pt`m@ni evolu\ie

eradicare chirurgie Urm`rire la 4 luni

Limfom cu celule mari

1. Chirurgie / chimioterapie2.ChimioterapieRxT/chirurgie

Limfom BurkittChimioterapie de urgen\`:

Doxorubicin`Ciclofosfamid`CytarabinaMty+ terapie integral`

Gastric Tumor Discovered by Chest RadiographyZalev AH, Kopplin PA. N Engl J Med 1999;340:927-927.

*Figure 1. An 88-year-old Japanese woman had a six-week history of black stools and fatigue. Her hemoglobin level was 6.7 g per deciliter, and a fecal occult-blood test (Hemoccult) was positive on two occasions. A chest x-ray film showed a round, soft-tissue mass (arrow in Panel A) within the gastric air bubble and no clinically significant intrathoracic abnormalities. An upper gastrointestinal series revealed a round, lobulated mass arising from the right lateral and posterior walls of the gastric fundus. A computed tomographic scan with oral and intravenous contrast medium revealed an intraluminal mass (arrow in Panel B) with a lower density than that of the adjacent wall and no evidence of extragastric extension. At endoscopy, an ulcerated tumor was found. The patient initially declined surgery because of her age. Two months later, however, after two episodes of acute gastrointestinal bleeding, a localized gastric resection was performed. Histologic analysis (Panel C) revealed an ulcerated, submucosal spindle-cell tumor that was negative for smooth-muscle or neural markers and positive for the filament marker vimentin (hematoxylin and eosin, 40). Because of an inability to demonstrate differentiation or the derivation of spindle cells, the mass was diagnosed as a gastrointestinal stromal tumor. Since surgery, the patient has had no further bleeding, and her hemoglobin level has increased to 12.7 g per deciliter.

*Table 1. U.S. Consensus Guidelines for Colonoscopic Surveillance after Polypectomy.*Figure 2. The Use of Endoscopic Landmarks to Distinguish Normal Esophagus (Panel A) from Barrett's Esophagus (Panel B).

The squamocolumnar junction, or Z line, is the visible line formed by the juxtaposition of squamous and columnar epithelia. The gastroesophageal junction is the imaginary line at which the esophagus ends and the stomach begins. The gastroesophageal junction is identified endoscopically as the most proximal part of the gastric folds. In normal esophagus, the squamocolumnar junction and gastroesophageal junction often coincide, and there is no columnar epithelium between the two (Panel A). The inset in Panel A shows normal stratified squamous epithelium. In Barrett's esophagus, the squamocolumnar junction is proximal to the gastroesophageal junction (Panel B). The area between the two junctions consists of columnar epithelium with specialized intestinal metaplasia (inset in Panel B). Modified from Spechler4 with the permission of the publisher. (Inset in Panel A, hematoxylin and eosin, x80; inset in Panel B, hematoxylin and eosin, x100.) Photomicrographs provided by Dr. Edward Lee.*Figure 1. Endoscopic Photograph Showing Traditional, or Long-Segment, Barrett's Esophagus.

Reddish, columnar epithelium extends more than 3 cm above the gastroesophageal junction.*Figure 2. Endoscopic Image (Panel A) and Endoscopic Ultrasonogram (Panel B) Showing a Transmural Adenocarcinoma of the Esophagus Associated with Barrett's Esophagus (Short Arrows), with Lymph-Node Metastases (Long Arrow).

Courtesy of John Saltzman, M.D.*Figure 5. Endoscopic Laser Therapy. Panel A shows the endoscopic appearance of the gastroesophageal junction in a patient with an adenocarcinoma causing near-total obstruction. The patient declined chemoradiation therapy and was not deemed a candidate for surgery, because of severe coexisting illness. In Panel B, the same area is shown after endoscopic laser photoablation of the tumor. Luminal patency had been restored. A hiatal hernia can be seen beyond the treated tumor.*A 37-year-old man was evaluated because of a two-year history of asymptomatic thickening and darkening of the skin on his axillae (Panel A), neck, face, and arms. The patient had no history of diabetes mellitus or other endocrine disorders, alcohol abuse, or chronic hepatitis. On examination of the skin, brown patches and plaques with elevated ridges and a velvety feel were observed on the axillary regions, the neck, the antecubital fossae, the dorsal aspect of the hands, and the malar and periorbital regions. Cutaneous findings were consistent with the diagnosis of acanthosis nigricans. An evaluation for cancer revealed a hepatic mass, 20 by 17 cm. The patient underwent right hepatic lobar resection. Histopathological examination of the resected tissue showed a moderately differentiated hepatocellular carcinoma with extensive hemorrhagic, necrotic, and sclerotic areas (T2N0M0). Three months after surgery, a spontaneous complete regression of cutaneous lesions occurred (Panel B). Malignant acanthosis nigricans is a rare form of acanthosis nigricans that precedes or occurs in association with often aggressive internal cancers and usually correlates with the evolution of the underlying neoplasm.*A 64-year-old man presented with a 6-month history of epigastric pain, weight loss, and nausea. In the previous 3 months, he had lost 10 kg. On examination, he was noted to have a nontender, firm, fixed, left supraclavicular lymph node measuring 3.0 by 2.5 cm. Upper endoscopy revealed an adenocarcinoma of the gastric corpus. Computed tomography of the abdomen showed liver metastasis. Virchow's node, or Troisier's node, refers to carcinomatous involvement of the supraclavicular nodes at the junction of the thoracic duct and the left subclavian vein. Usually, nodal enlargement is caused by metastatic gastric carcinoma, although supraclavicular nodal involvement can also be seen in other gastrointestinal, thoracic, and pelvic cancers. Gastric cancers tend to metastasize to this region by means of migration of tumor emboli through the thoracic duct, where subdiaphragmatic lymphatic drainage enters the venous circulation in the left subclavian vein. Given the patient's low performance status, according to his Karnofsky performance-status score and his score on the Eastern Cooperative Oncology Group Performance Status scale, chemotherapy was contraindicated, and he was referred for palliative radiotherapy.*Figure 1. An 88-year-old Japanese woman had a six-week history of black stools and fatigue. Her hemoglobin level was 6.7 g per deciliter, and a fecal occult-blood test (Hemoccult) was positive on two occasions. A chest x-ray film showed a round, soft-tissue mass (arrow in Panel A) within the gastric air bubble and no clinically significant intrathoracic abnormalities. An upper gastrointestinal series revealed a round, lobulated mass arising from the right lateral and posterior walls of the gastric fundus. A computed tomographic scan with oral and intravenous contrast medium revealed an intraluminal mass (arrow in Panel B) with a lower density than that of the adjacent wall and no evidence of extragastric extension. At endoscopy, an ulcerated tumor was found. The patient initially declined surgery because of her age. Two months later, however, after two episodes of acute gastrointestinal bleeding, a localized gastric resection was performed. Histologic analysis (Panel C) revealed an ulcerated, submucosal spindle-cell tumor that was negative for smooth-muscle or neural markers and positive for the filament marker vimentin (hematoxylin and eosin, 40). Because of an inability to demonstrate differentiation or the derivation of spindle cells, the mass was diagnosed as a gastrointestinal stromal tumor. Since surgery, the patient has had no further bleeding, and her hemoglobin level has increased to 12.7 g per deciliter.