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Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 271 records · Page 15Linked to original sources
PubMed1998

Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide.

The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways.

Amino Acid Sequence↗
PubMed1998

Unique organization and involvement of GAGA factors in transcriptional regulation of the Xenopus stromelysin-3 gene.

Expression of the matrix metalloproteinase (MMP) gene stromelysin-3 ( ST3 ) has been shown to be tightly associated with cell migration and apoptosis inmammals and amphibians. This contrasts with most other MMP genes. We demonstrate here that the Xenopus ST3 gene also has a structure distinct from other MMP genes, with its C-terminal half (the hemopexin domain) encoded by 4 instead of 6 exons, as in other MMP genes. Our primer extension analysis reveals the existence of two transcription start sites and at least one is needed for transcription of the promoter in transient transfection assays. Furthermore, our deletion analysis has demonstrated a requirement for at least one GAGA factor binding site for promoter function. In vitro DNA binding and mutational studies have provided strong evidence for the participation of GAGA or GAGA-like factors in transcriptional regulation of the frog ST3 gene. This contrasts with regulation of the human ST3 promoter. These results suggest that the ST3 gene evolved prior to most other metalloproteinase genes and uses distinct regulation pathways to achieve similar expression profiles and serve similar functions in mammals and amphibians.

Animals↗
PubMed1998

Transcription from the thyroid hormone-dependent promoter of the Xenopus laevis thyroid hormone receptor betaA gene requires a novel upstream element and the initiator, but not a TATA Box.

The thyroid hormone receptor (TR) beta genes in Xenopus laevis are regulated by thyroid hormone in all organs of an animal during metamorphosis. This autoregulation appears to be critical for systematic transformations of different organs as a tadpole is transformed into a frog. To understand this autoregulation, we have previously identified a thyroid hormone response element in the hormone-dependent promoter of the X. laevis TRbetaA gene. We report here the detailed characterization of the promoter. We have now mapped the transcription start site and demonstrated the existence of an initiator element at the start site critical for promoter function. More important, our deletion and mutational experiments revealed a novel upstream DNA element that is located 125 base pairs upstream of the start site and that is essential for active transcription from the promoter. Promoter reconstitution experiments showed that this novel element does not function as an enhancer, but acts as a core promoter element, which, together with the initiator, directs accurate transcription from the promoter. Finally, we provide evidence for the existence of a protein(s) that specifically recognizes this element. Our studies thus demonstrate that the TRbetaA promoter has a unique organization consisting of an initiator and a novel upstream promoter element. Such an organization may be important for the ubiquitous but tissue-dependent temporal regulation of the gene by thyroid hormone during amphibian metamorphosis.

Animals↗
PubMed1998

The use of adaptive radiation therapy to reduce setup error: a prospective clinical study.

PURPOSE: Adaptive Radiation Therapy (ART) is a feedback treatment process that optimizes a patient's treatment according to the patient specific information measured during the course of treatment. Utilizing an electronic portal imaging device (EPID) and a computer-controlled multileaf collimator (MLC), the ART process is currently being implemented in our clinic to improve the treatment accuracy by compensating for the treatment setup error. A prospective study was conducted to evaluate the feasibility and efficacy of the ART process for clinical use. METHODS AND MATERIALS: The prospective study included 20 patients who underwent conventional radiotherapy on a linear accelerator equipped with an EPID and a MLC. No specific changes were made in the routine clinical procedures except daily portal images were obtained for each treatment field. Two-dimensional setup error for each treatment field was then measured offline using a software tool. The measured setup errors from initial treatment days were used to predict the systematic and random setup errors for each treatment field. An adjustment decision was made if the predicted systematic error was larger than or equal to 2 mm. Furthermore, the treatment field was extended if the predicted random setup error could not be effectively compensated by the predefined treatment setup margin. Instead of the conventional approach of patient repositioning, setup adjustment was implemented by reshaping the MLC field. The entire process from measuring setup error to reshaping the MLC field was performed offline through a computer network. After completion of a patient's treatment, the systematic and random setup errors after adjustment were compared with those predicted prior to the adjustment. The accuracy of the adjustment, and the reliability and stability of the process were analyzed. RESULTS: Treatment fields of 13 patients were modified to correct for systematic errors. The mean systematic error was 4 mm with a range of 2 to 7 mm before adjustment. It was reduced to 0.5 mm with a range of 0.2 to 1.4 mm after adjustment. There was no significant difference in random setup errors before and after adjustment. The ART process was found to be stable, as more than 95% of patient specific setup margins were predictable within 1 mm using the first four to nine fractions of treatment, confirming the feasibility of treatment plan reoptimization with the ART process. CONCLUSIONS: The prospective study demonstrates that the ART process can be effectively implemented in routine clinical practice to improve treatment accuracy. This process is also ready to be further extended to reoptimize the treatment plan by incorporating the predicted patient specific setup variation.

Feasibility Studies↗
PubMed1998

Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.

The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is expressed in glomerular podocytes during a narrow window in kidney development. By immunoprecipitation and protein microsequencing analysis, we have identified a major cellular protein associated with endogenous WT1 to be the inducible chaperone Hsp70. WT1 and Hsp70 are physically associated in embryonic rat kidney cells, in primary Wilms tumor specimens and in cultured cells with inducible expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of the developing kidney, and Hsp70 is recruited to the characteristic subnuclear clusters that contain WT1. The amino-terminal transactivation domain of WT1 is required for binding to Hsp70, and expression of that domain itself is sufficient to induce expression of Hsp70 through the heat shock element (HSE). Substitution of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to restore the functional properties of a WT1 protein with an amino-terminal deletion, an effect that is abrogated by a point mutation in DNAJ that reduces binding to Hsp70. These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation.

Amino Acid Sequence↗
PubMed1998

Unusual features of the Drosophila melanogaster telomere transposable element HeT-A are conserved in Drosophila yakuba telomere elements.

HeT-A was the first transposable element shown to have a bona fide role in chromosome structure, maintenance of telomeres in Drosophila melanogaster. HeT-A has hallmarks of non-long-terminal-repeat (non-LTR) retrotransposable elements but also has several unique features. We have now isolated HeT-A elements from Drosophila yakuba, showing that the retrotransposon mechanism of telomere maintenance predates the separation of D. melanogaster and D. yakuba (5-15 million years ago). HeT-A elements from the two species show significant sequence divergence, yet unusual features seen in HeT-Amel are conserved in HeT-Ayak. In both species, HeT-A elements are found in head-to-tail tandem arrays in telomeric heterochromatin. In both species, nearly half of the HeT-A sequence is noncoding and shows a distinctive imperfect repeat pattern of A-rich segments. Neither element encodes reverse transcriptase. The HeT-Amel promoter appears to be intermediate between the promoters of non-LTR and of LTR retrotransposons. The HeT-Ayak promoter shows similar features. HeT-Amel has a frameshift within the coding region. HeT-Ayak does not require a frameshift but shows conservation of the polypeptide sequence of the frameshifted product of D. melanogaster.

Animals↗
PubMed1998

A critical temporal requirement for the retinoblastoma protein family during neuronal determination.

In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing neocortex. To determine whether pRb is required for neuronal determination in vivo, we crossed the Rb-/- mice with transgenic mice expressing beta-galactosidase from the early, panneuronal Talpha1 alpha-tubulin promoter (Talpha1:nlacZ). In E12.5 Rb-/- embryos, the Talpha1:nlacZ transgene was robustly expressed throughout the developing nervous system. However, by E14. 5, there were perturbations in Talpha1:nlacZ expression throughout the nervous system, including deficits in the forebrain and retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus E1A protein. These studies revealed that induction of Talpha1:nlacZ did not require proteins of the pRb family. However, in their absence, determined, Talpha1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of "mixed signals" deriving from their inability to undergo terminal mitosis. In contrast, when the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it cause the postmitotic neurons to reenter the cell cycle. Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but are essential for determined neurons to exit the cell cycle and survive.

Animals↗
PubMed1998

Mismatch repair co-opted by hypermutation.

Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.

Adenosine Triphosphatases↗
PubMed1998

Distinct requirements for chromatin assembly in transcriptional repression by thyroid hormone receptor and histone deacetylase.

Histone deacetylase and chromatin assembly contribute to the control of transcription of the Xenopus TRbetaA gene promoter by the heterodimer of Xenopus thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). Addition of the histone deacetylase inhibitor Trichostatin A (TSA) relieves repression of transcription due to chromatin assembly following microinjection of templates into Xenopus oocyte nuclei, and eliminates regulation of transcription by TR-RXR. Expression of Xenopus RPD3p, the catalytic subunit of histone deacetylase, represses the TRbetaA promoter, but only after efficient assembly of the template into nucleosomes. In contrast, the unliganded TR-RXR represses templates only partially assembled into nucleosomes; addition of TSA also relieves this transcriptional repression. This result indicates the distinct requirements for chromatin assembly in mediating transcriptional repression by the deacetylase alone, compared with those needed in the presence of unliganded TR-RXR. In addition, whereas hormone-bound TR-RXR targets chromatin disruption as assayed through changes in minichromosome topology and loss of a regular nucleosomal ladder on micrococcal nuclease digestion, addition of TSA relieves transcriptional repression but does not disrupt chromatin. Thus, TR-RXR can facilitate transcriptional repression in the absence of hormone through mechanisms in addition to recruitment of deacetylase, and disrupts chromatin structure through mechanisms in addition to the inhibition or release of deacetylase.

Amino Acid Sequence↗
PubMed1998

Biliary complications after hepatic resection: risk factors, management, and outcome.

OBJECTIVE: To identify the risk factors for the development of biliary complications after hepatic resection and to evaluate management in relation to the outcomes of these patients. DESIGN: Biliary complications are a common cause of major morbidity after hepatic resection. A survey was made of all patients undergoing hepatic resection at 1 institution. Perioperative risk factors related to the development of biliary complications were identified using multivariate analysis. Management and outcome were analyzed also. SETTING: A tertiary referral center. PATIENTS: From January 1, 1989, to October 31, 1995, 347 consecutive patients underwent 229 major and 118 minor hepatic resections. MAIN OUTCOME MEASURE: Development of postoperative biliary complications. RESULTS: Biliary complications developed in 28 (8.1%) of 347 patients; these complications carried high risks for liver failure (35.7%) and operative mortality (39.3%). Stepwise logistic regression analysis identified increasing age, higher preoperative white blood cell count, left-sided hepatectomy, and prolonged operation time as the independent predictors of development of biliary complications. Conservative treatment or nonoperative measures alone, such as percutaneous drainage or endoscopic therapy, were effective in treating the complication in 13 of 19 patients, but those who required reoperation had a high mortality rate (7 [77.8%] of 9 patients). Patients with demonstrable leakage from the common bile duct or its bifurcation tended to have poor outcomes. CONCLUSIONS: Biliary complications are a common and serious cause of morbidity after hepatic resection. Preresection cholangiography for finding biliary tract anomaly is recommended before left-sided hepatectomy. Although nonoperative measures are the preferred approach for selected patients with biliary complications, those with demonstrable leakage from the common bile duct or its bifurcation have a grave prognosis and may benefit from early surgical intervention.

Adult↗
PubMed1998

Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial.

OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.

Antineoplastic Agents↗
PubMed1998

Quality of life in patients with cancer of the esophagus and gastric cardia: a case for palliative resection.

OBJECTIVE: To evaluate quality-of-life (QOL) parameters in patients undergoing esophagectomy, curative or palliative, for carcinoma. DESIGN: Nonconsecutive case series. PATIENTS: Eighty-eight patients who underwent esophagectomy for cancer (curative, n=49 [56%]; palliative, n=39 [44%]) provided QOL assessments over an 18-month period. SETTING: Procedures for referral care were performed by a single team of clinicians in a tertiary referral center. Evaluations of QOL were made by 1 independent trained investigator. OUTCOME MEASURES: Data were documented by questionnaire at interview and parameters evaluated included an esophageal module for the type and quantity of food intake, severity of related symptoms on eating, Eastern Cooperative Oncology Groups (ECOG) performance status, sleep, pain, leisure activity, working capacity, outlook on life, general well-being, and support from family and friends. A summation of selected parameters was used to calculate a total score. RESULTS: Significant improvements were recorded in both the curative and palliative groups for at least 1 year following surgery in the type (P<.03) and quantity (P<.03) of food intake and severity of diet-related symptoms (P<.02), when compared with preoperative considerations. Findings were comparable between the groups with regard to dietary intake. Pain status and total scores were worse in the palliative group at 9 months postoperatively but no significant differences between the groups were evident at any time for sleep, leisure activity, and ECOG performance status. CONCLUSIONS: To our knowledge, there are no previous data regarding a comparison of QOL considerations in patients who have undergone either potentially curative or palliative esophagectomy for malignant disease. Data analysis revealed that palliative esophagectomy provided enhanced QOL with marked symptomatic benefits and enjoyment of daily living comparable to that observed following curative resection.

Cardia↗
PubMed1998

Current status of pharyngolaryngo-esophagectomy and pharyngogastric anastomosis.

BACKGROUND: Pharyngolaryngo-esophagectomy and pharyngogastric anastomosis (PLO & PGA) is one of the surgical options in the management of tumors arising from the hypopharynx and cervical esophagus. Indications of the operation and the outcome are changing over the years. To examine these, the experience of this operation in one Institute (the Head and Neck Division of the Department of Surgery, The University of Hong Kong at Queen Mary Hospital, Hong Kong) over the last 30 years was reviewed. METHODS: From 1966 to 1995, a total of 317 patients underwent PLO & PGA. The clinical results of 69 patients operated on between 1986 and 1995 were analyzed and compared with those of the two groups of patients reported previously from the same Institute to establish the current status of PLO & PGA. RESULTS: The demographic data of three groups of patients were similar. In previous years, 53% of the primary tumors were advanced laryngeal carcinomas extending to the hypopharynx, whereas the other 47% originated from hypopharyngeal and cervical esophageal regions. In recent years, all patients belonged to the latter group. CONCLUSIONS: The hospital mortality has decreased from 31% to 9%, and the incidence of morbidity such as anastomotic leakage and bleeding has also been reduced, from 20% to 10%. This may be related to the introduction of transthoracic endoscopic mobilization of the esophagus and patient selection. The overall minor morbidity has, however, remained at about 49%, and the 5-year actuarial survival rate has improved, from 18% in the 1970s to 24.5% at present.

Adult↗
PubMed1998

Primary biliary stones: diagnosis and management.

To review the results of treatment of primary biliary stones, 96 consecutive patients managed from 1991 to 1996 were studied retrospectively. Acute cholangitis and abdominal pain were the presenting symptoms in 57 patients (59%) and 29 patients (30%), respectively. Fifty-four patients (56%) had a history of biliary surgery. Endoscopic retrograde cholangiopancreatography, ultrasonography, and computed tomography were frequently employed for diagnosis of primary biliary stones and were performed on 84 patients (88%), 90 patients (94%), and 89 patients (93%), respectively. Intrahepatic stones were identified in 91 patients (95%) and biliary strictures in 34 patients (35%). Concomitant cholangiocarcinoma occurred in 15 patients (16%). Hepatic resection was required in 55 patients (57%) for removal of an atrophic liver lobe or a segment related to repeated infection, biliary strictures, liver abscesses, or cholangiocarcinoma. Intraoperative choledochoscopy was routinely performed in all patients to detect, remove, or confirm clearance of biliary stones. A hepaticocutaneous jejunostomy (HCJ) was constructed in 70 patients (73%) to facilitate postoperative choledochoscopic examination or biliary stone extraction. Twenty-two patients (23%) had residual stones and required postoperative choledochoscopic extraction. Complete eradication of residual stones was achieved in all patients. Postoperative morbidity occurred in 28 patients (29%), and there was one hospital death (a patient with cholangiocarcinoma). With a median follow-up of 26 months (range 2-62 months), stones recurred in three patients. In conclusion, the early results of treatment of primary biliary stones were satisfactory owing to a systematic, aggressive approach that consisted of hepatic resection, frequent construction of an HCJ, and postoperative choledochoscopy.

Adult↗
PubMed1998

Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo.

UNLABELLED: The DNA topoisomerases I and II are the target of several clinically important antineoplastic agents which produce DNA cleavage by stabilization of the covalent DNA-protein bond with resultant cell death after DNA synthesis is attempted. Depletion of the target topoisomerase and reciprocal changes in the other occur with drug treatment. PURPOSE AND METHODS: To develop empiric treatment regimens of combinations and sequences of agents directed against topoisomerase I (irinotecan/CPT-11) and II (etoposide and doxorubicin), in vivo studies were performed in mice bearing the EMT-6 mammary tumor to assess efficacy, host tolerance and the resultant biochemical changes in topoisomerase mRNA and protein. RESULTS: At 24 h after therapy, depletion of the target topoisomerase mRNA and protein with reciprocal increases in the alternate topoisomerase mRNA and, to a lesser extent, protein were noted. No therapeutic antagonism was found with any combination or sequence of agents, and therapeutic antagonism was noted with concurrent irinotecan/etoposide and sequential doxorubicin/irinotecan. Depletion of target topoisomerases by combined therapy beyond a threshold necessary for therapeutic efficacy produced no additional benefit. CONCLUSIONS: Antineoplastic therapy with combinations of topoisomerase I and II agents is feasible and may produce therapeutic synergy. The appropriate sequence may depend on the particular agents used. The rationale for such therapy, that topoisomerases I and II may have reciprocal and compensatory interactions, is supported by the biochemical data.

Animals↗
PubMed1998

The significance of histologically infiltrated resection margin after esophagectomy for esophageal cancer.

BACKGROUND: Microscopic tumor infiltration of the resection margin after esophageal resection is implicated to influence anastomotic leakage, tumor recurrence rates, and long-term survival. METHODS: Patients with tumor infiltration of resection margin (RM+) and those without (RM-) were compared. RESULTS: Of 604 patients, 45 (7.5%) were RM+. Patients in the RM+ group had more palliative resections, 76% versus 56%, P = 0.01. Anastomotic leakage rates were 2.2% (RM+) and 4.1% (RM-), P = 1.0. Excluding hospital deaths, anastomotic recurrences developed in 10.3% in the RM+ group and 4.9% in the RM- groups, P = 0.15. Although a positive margin did not increase anastomotic recurrence, a shorter resection margin correlated with such recurrence. The mean (SEM) lengths of resection margins in surgical specimens were 2.7 cm (0.3) and 4.4 cm (0.1) for those with and without recurrence, P < 0.001. Median survival time were 8.8 months (RM+) and 15 months (RM-), P = 0.007. CONCLUSIONS: Histologic infiltration of resection margins did not influence leakage rate. Anastomotic recurrence was related to the length of resection margin.

Adult↗
PubMed1998

Multiple primary cancers in esophageal squamous cell carcinoma: incidence and implications.

BACKGROUND: The occurrence of multiple primary cancers in the aerodigestive tract is a well-known phenomenon. This study aims to elucidate the incidence and the therapeutic and prognostic implications of a nonesophageal primary cancer in patients with squamous cell carcinoma of the esophagus. METHODS: Between 1982 and 1996, 1,055 patients with esophageal squamous cell carcinoma treated at our institution were reviewed for the presence of an additional primary cancer. The effects of the nonesophageal cancer on treatment of the esophageal carcinoma and survival were analyzed. RESULTS: Among 1,055 patients, 114 nonesophageal primary cancers were documented in 100 patients (9.5%), 70% of which were aerodigestive tract cancers. Forty-seven patients had antecedent tumors and 43 had synchronous tumors. Treatment strategies for esophageal carcinoma in these patients were similar to patients without multiple tumors, not influenced by the nonesophageal tumor except in 6 patients. The overall survival of patients with antecedent tumors, synchronous tumors, and without multiple tumors was similar (median survival, 8.6, 8.5, and 8.8 months, respectively) (p = 0.84). Subsequent primary cancers developed in 10 patients (0.9%), 9 of them with previous curative resection of esophageal cancer, and all died of the subsequent cancer. CONCLUSIONS: There is a high incidence of multiple primary cancers in patients with esophageal carcinoma but the treatment and prognosis of these patients are primarily determined by the esophageal carcinoma itself. Subsequent cancer is, however, a significant cause of death among patients cured of esophageal carcinoma.

Alcohol Drinking↗