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Docetaxel-based combined-modality chemoradiotherapy for locally advanced non-small cell lung cancer.

The cytotoxic agent docetaxel not only has proven activity in non-small cell lung cancer-when used alone or in combination-but is also a potent radiosensitizer, and improved treatments are needed in all stages of this disease. In patients with locoregionally advanced (stage III) disease, docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy/surgery. Presently, therapeutic gains appear to be maximized by the use of concurrent chemotherapy and irradiation. This review focuses on research with combinations of docetaxel with either cisplatin or carboplatin and radiotherapy. Overall response and survival rates to date provide data worth pursuing. From phase I data, weekly docetaxel at 20 mg/m(2) plus cisplatin at 25 mg/m(2) or carboplatin to an area under the concentration time curve of 2 mg/ml*min with concurrent radiotherapy to 60 Gy over 6 weeks appear to be suitable for phase II trials. Predominant toxicities are esophagitis and neutropenia, but a low frequency of pulmonary toxicity is reported. Induction, concurrent, and consolidation docetaxel-based chemoradiotherapy in potentially resectable disease are all being investigated. Future research could include the investigation of computed tomography/ positron emission tomography-derived target volume radiotherapy, dose-escalated therapy, and alternative fractionation schedules in combination with docetaxel-based cytotoxic chemotherapy.

Aged↗

Effect of data collection method on results of serum digoxin concentration audit.

The appropriateness of serum digoxin concentration (SDC) orders was evaluated with respect to indication for use, sampling time, and action taken by physicians when the reported SDC was out of the normal therapeutic range; the effect of the two data-collection methods used (retrospective and concurrent audits) on the results was studied. Criteria for the appropriate use of SDCs were approved by the medical staff through the pharmacy and therapeutics committee. Patients on adult medicine services were entered into the study as daily SDC determinations were reported by the clinical laboratory. Most of the SDCs were evaluated using approved criteria by primary pharmacist clinicians who were concurrently monitoring drug therapy and participating with the treatment team. A retrospective audit of the same patients was conducted, using only chart review. A total of 134 SDCs involving 78 patients were evaluated. Concurrent-audit results indicated that 18.7% of the SDCs were ordered without an appropriate indication, 16.4% were sampled incorrectly with respect to proper timing, and 8.2% did not result in dosage adjustments when indicated. With respect to appropriate sampling time and overall use of SDCs, significantly more SDCs met the standards under concurrent audit than under retrospective audit. The retrospective chart review method of auditing may not detect as much pertinent information as is desirable.

Concurrent Review↗

Mathematical review of literature to assess alternative electron transports and interphotosystem excitation partitioning of steady-state C3 photosynthesis under limiting light.

Linear whole-chain electron (e(-)) transport plays a dominant role in generating NADPH and ATP required for carbon fixation in chloroplasts. However, other e(-) pathways may be present to contribute to the flexibility of e(-) transport in meeting demands by various downstream metabolic processes. The estimation of the fluxes of these alternative pathways in vivo is difficult, as they are not amenable to direct experimental measurement. A recently developed model based on the generalized stoichiometry for the chloroplast e(-) transport pathways makes it possible to indirectly but quantitatively assess the fractions of e(-) that follow the alternative pathways. This model approach is used to review data from the literature on concurrent measurements of gas exchange and chlorophyll (Chl) fluorescence under steady-state, limiting light, non-photorespiratory conditions. The review suggests possible in vivo occurrence of cyclic e(-) transport (CET) under such conditions. About 10% of e(-) from the reduced ferredoxin follow the pseudocyclic mode, notably in support of nitrate reduction. The estimated fraction of e(-) from the reduced plastoquinone that follows the Q-cycle ( f(Q)) depends on the number of protons required per ATP synthesis. Our model approach also allows the excitation partitioning to photosystem II (PSII) to be assessed quantitatively. Most important, the model helps assess the limit value to uncertain physiological parameters and answer the 'what-if' question with regard to the effect of non-measured processes or measurement uncertainties on the estimations of alternative e(-) transports.

Electron Transport↗

Concurrent chemoradiotherapy in non-small cell lung cancer.

BACKGROUND: In a previous meta-analysis of adjuvant chemotherapy in NSCLC there was a 13% reduction in the risk of death in patients receiving radical radiotherapy. This overview specifically excluded trials in which chemotherapy and radiotherapy were given concurrently (NSCLCCG 1995). The use of concurrent chemotherapy and radiotherapy might be seen as a way of increasing the effectiveness of radiotherapy at the same time as reducing the risks of metastatic disease by using chemotherapy. OBJECTIVES: To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to local control and overall survival; and to determine whether the addition of concurrent chemotherapy results in an altered risk of treatment-related morbidity. To compare concurrent with sequential chemoradiotherapy. SEARCH STRATEGY: Electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE with identification of further studies from references cited in the initial identified studies. SELECTION CRITERIA: Randomised trials of patients with stage I-III non-small cell lung cancer (NSCLC) undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy. DATA COLLECTION AND ANALYSIS: Identified trials were reviewed independently by both reviewers. Relative risks (calculated according to a random-effects model) were determined with respect to overall survival, progression-free survival and treatment morbidity. MAIN RESULTS: Fourteen randomised studies (including 2393 patients) of concurrent chemoradiotherapy versus radiotherapy alone met the inclusion criteria. In a meta-analysis there was a reduction in risk of death at two years (relative risk (RR) 0.93; 95% CI 0.88 to 0.98; P = 0.01). Similar improvements in two-year locoregional progression-free survival (RR 0.84; 95% CI 0.72 to 0.98; P = 0.03) and progression-free survival at any site (RR 0.90; 95% CI 0.84 to 0.97; P = 0.005) were also seen in those receiving concurrent chemoradiotherapy. Subgroup analysis suggested the possibility of a greater benefit from regimens which incorporated once daily fractionation of radiotherapy or a higher total chemotherapy dose. The incidence of acute oesophagitis, neutropenia and anaemia were significantly increased by concurrent chemoradiotherapy. In a meta-analysis of three trials of concurrent versus sequential chemoradiotherapy there was a significant reduction in the risk of death at two years with concurrent treatment (RR 0.86; 95% CI 0.78 to 0.95; P = 0.003) but potentially at the expense of toxicity, although data was incomplete. REVIEWERS' CONCLUSIONS: With concurrent chemoradiotherapy there was a 14% reduction in risk of death at two years compared to sequential chemoradiotherapy, and a 7% reduction compared to radiotherapy alone. In both cases there was some increase in acute oesophagitis. Caution is advised in adopting concurrent chemoradiotherapy as the standard of care because of uncertainties about the true magnitude of benefit in comparison with sequential chemoradiotherapy. With short follow up and uncertainties about toxicity in the identified studies, the optimal chemotherapy regimen remains uncertain. The confounding effects of treatment-related anaemia and gaps in treatment due to toxicity require further investigation.

Antineoplastic Combined Chemotherapy Protocols↗

Non-syndromic association of congenital hepatic fibrosis and bilateral cystic renal dysplasia.

Congenital hepatic fibrosis (CHF) is associated with autosomal recessive polycystic kidney disease (ARPKD). Although cystic renal dysplasia (CRD) is the most common form of newborn cystic renal disease, this disorder of anomalous metanephric differentiation is only rarely found concurrent with CHF. Our literature review found only 13 sporadic and 12 familial non-syndromic cases of combined bilateral CRD and CHF reported outside Taiwan. We report the first domestic case, occurring in a fetus of 18 weeks' gestational age, which was the second pregnancy of a 24-year-old mother with a previous history of spontaneous abortion at 10 weeks' gestational age. Postmortem autopsy confirmed the concurrence of bilateral CRD and CHF without associated anomalies of other visceral organs and external appearance. This particular association must be differentiated from ARPKD and liver disease, in regard to ultrasonographic examination and genetic counseling.

Adult↗

Concurrent ifosfamide-based chemotherapy and irradiation. Analysis of treatment-related toxicity in 43 patients with sarcoma.

BACKGROUND: The current study was performed to evaluate the toxicity profile of therapeutic doses of ifosfamide (IFX) given concurrently with full-dose external beam radiotherapy (EBRT) in patients with soft tissue and bone sarcomas. METHODS: The medical records of 43 consecutive patients with soft tissue or bone sarcomas who were treated with concurrent IFX and EBRT were reviewed. RESULTS: The median patient age was 20 years. Histologies were rhabdomyosarcoma (n = 16 patients), Ewing sarcoma (n = 10 patients), malignant fibrous histiocytoma (n = 9 patients), and other soft tissue sarcomas (n = 8 patients). Thirty-one patients (72%) had localized disease, and 12 patients (28%) had synchronous local and distant disease. Treatment consisted of EBRT (median dose, 50.4 gray [Gy]) with concomitant IFX (median dose per cycle, 10.2 g/m(2)). All patients with Ewing sarcoma or rhabdomyosarcoma received additional concurrent chemotherapy. Twenty-six patients (60%) received two or more cycles of IFX, and 17 patients (40%) were treated with one cycle of IFX and EBRT. The incidences of World Health Organization Grade 3 and Grade 4 toxicities were 29% (21 of 73 cycles) and 22% (16 of 73 cycles), respectively. Grade 4 systemic toxicities included leukopenia (n = 14 patients), neurotoxicity (suicidal ideation; n = 1 patient), and diarrhea (n = 1 patient). Confluent moist desquamation (Grade 3) occurred in nine patients in the treatment field; no patient experienced Grade 4 local toxicity. Among 14 patients who were treated preoperatively, 2 patients (14%) had a pathologic complete response, and 6 patients (43%) had a pathologic near-complete response (> or = 90% necrosis). CONCLUSIONS: Local and systemic toxicities after the administration of therapeutic doses of IFX with concomitant EBRT appear comparable to those observed with either treatment alone. These results support the design of prospective studies evaluating concurrent ifosfamide and radiation therapy for patients with sarcomas.

Adult↗

Hodgkin's lymphoma in an adolescent with systemic lupus erythematosus.

An adolescent female with systemic lupus erythematosus (SLE) with diffuse proliferative lupus nephritis subsequently contracted Hodgkin's lymphoma, mixed cellularity type. Prior to the diagnosis of Hodgkin's lymphoma, hypogammaglobulinemia developed with IgG deficiency. The nephritis, which improved on steroid therapy, remitted entirely after nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) therapy. The hypogammaglobulinemia also remitted after chemotherapy for Hodgkin's lymphoma. The literature concerning the association of SLE and Hodgkin's lymphoma is reviewed. The significance of this concurrence is discussed in regard to the possible pathophysiology and the clinical management.

Adolescent↗

Extensive posterior-lateral tracheal laceration complicating percutaneous dilational tracheostomy.

BACKGROUND: An extensive posterior-lateral longitudinal tracheal laceration is an uncommon but serious complication of percutaneous dilational tracheostomy (PDT). We report the successful management of three ventilator-dependent patients whose percutaneous tracheostomy was complicated by an extensive longitudinal posterior-lateral tracheal laceration requiring operative repair. METHODS: A retrospective review of 134 cases of PDT with concurrent bronchoscopy was performed between April 1997 and July 1999 and compared with a review of 124 cases of open tracheostomy. Tracheal lacerations were primarily repaired and augmented with intercostal muscle pedicle buttress. RESULTS: Three cases of an extensive posterior-lateral longitudinal tracheal laceration that required operative repair were reported in the PDT group. None were reported in the open tracheostomy group. The 3 patients were managed with an adult high-frequency oscillating ventilator or pressure control ventilation during the postoperative period to limit barotrauma, and all healed without evidence of tracheal leak or stenosis. CONCLUSIONS: The increasing popularity of PDT, particularly among nonsurgical disciplines, may generate an increasing number of complications requiring operative attention. Thoracic surgeons need to be cognizant of the pitfalls of PDT technique and be prepared to manage these difficult clinical scenarios.

Adult↗

Distinguishing fatigue and depression in patients with cancer.

In seeking to learn more about the etiology and treatment of fatigue in patients with cancer, clinicians and researchers have been challenged to understand how fatigue can be distinguished from depression. Approaches currently used to study fatigue and depression in patients with cancer appear to be of limited usefulness in distinguishing these phenomena. This conclusion is supported by a review of studies in which the single-symptom and symptom-cluster approaches were used to measure fatigue and depression concurrently in patients with cancer. The review yielded consistent evidence of high positive correlations between fatigue and depression, even when attempts were made to eliminate overlapping item content. A consideration of causal mechanisms suggests why it remains difficult to distinguish between fatigue and depression. In addition to fatigue being a possible cause of depression and depression being a possible cause of fatigue, both fatigue and depression can share a common cause. That is, certain forms of cancer and cancer treatment can cause both fatigue and depression. These different mechanisms have implications for efforts to distinguish fatigue and depression and to identify appropriate treatments. For example, recently developed diagnostic criteria for a clinical syndrome of cancer-related fatigue might be useful in identifying fatigue that is caused by a major depressive disorder for which antidepressant therapy is generally indicated.

Depressive Disorder↗

Concurrent gastric bypass and repair of anterior abdominal wall hernias.

BACKGROUND: Many patients seeking surgical treatment for morbid obesity present with anterior abdominal wall hernias. Although principles of hernia repair involve a tension-free repair with the use of prosthetic mesh, there is concern about the use of mesh in gastric bypass surgery due to potential contamination with the contents of the gastrointestinal tract and resultant mesh infection. We report our series of patients undergoing Roux-en-Y gastric bypass (RYGBP) and simultaneous anterior abdominal wall hernia repair. METHODS: All patients who underwent simultaneous RYGBP surgery and anterior abdominal wall hernia repair were reviewed. RESULTS: 12 patients underwent concurrent RYGBP and anterior wall hernia repair. There were 5 women and 7 men with average age 54.9 +/- 8.5 years (range 35 to 64) and average body mass index (BMI) 50.4 +/- 10.3 kg/m(2) (range 38 to 70). Two open and 10 laparoscopic RYGBP operations were performed. Nine patients (75%) underwent incisional hernia repairs and 3 patients (25%) underwent umbilical hernia repair concurrent with gastric bypass. Average size of defect was 14.7 +/- 13.4 cm(2). One patient had primary repair and 11 patients had prosthetic mesh repair: polypropylene in 3 patients (25%) and polyester in 8 patients (67%). With a 14.1 +/- 9.3 month follow-up, there have been no mesh infections and 2 recurrences, one in the patient who underwent primary repair and one in a patient repaired with polyester mesh but with two previous failed incisional hernia repairs. CONCLUSION: Concurrent RYGBP and repair of anterior abdominal wall hernias is safe and feasible. In order to optimize success, tension-free principles of hernia repair with the use of prosthetic mesh should be followed since no mesh infections occurred in our series.

Adult↗

Inclusion body myositis and renal cell carcinoma. Report of two cases and review of the literature.

OBJECTIVE: To describe the clinical course of 2 patients with concurrent inclusion body myositis and renal cell carcinoma and review published reports of inclusion body myositis associated with malignancy. METHODS: Prospective followup of 2 patients. Review of published case reports and series of patients with inclusion body myositis. RESULTS: Our 2 patients with inclusion body myositis and renal cell carcinoma had no improvement of strength following nephrectomy. Seven previously reported cases of inclusion body myositis and malignancy were identified and are discussed. CONCLUSION: Findings in our 2 patients suggest that there is no etiopathologic relationship between inclusion body myositis and malignancy.

Carcinoma, Renal Cell↗

Management of blunt splenic injury in patients with concurrent infectious mononucleosis.

Selective nonoperative management is appropriate for most blunt splenic injuries in adults and children, but the efficacy of this approach is unknown when injury occurs in patients with concurrent infectious mononucleosis. We have reviewed our experience during the past 23 years with the selective nonoperative management of blunt splenic injury in these patients. Medical record review identified nine patients with blunt splenic injury and infectious mononucleosis from 1978 to 2001, representing 3.3 per cent of our total trauma population with blunt splenic injury treated during that interval. Two patients underwent immediate splenectomy because of hemodynamic instability. Seven patients were admitted with the intent to treat nonoperatively. Five patients were successfully managed nonoperatively. Two patients failed nonoperative management and underwent splenectomy, one because of hemodynamic instability and one because of an infected splenic hematoma. Concurrent infectious mononucleosis does not preclude the successful nonoperative management of blunt splenic injury. This small subset of patients may be managed nonoperatively using the same criteria as for patients whose splenic injuries are not complicated by infectious mononucleosis.

Adolescent↗

Progress in concurrent analysis of loss of heterozygosity and comparative genomic hybridization utilizing high density single nucleotide polymorphism arrays.

Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechanisms underlying many medical disorders. Analysis of chromosomal aberrations is particularly important in cancer research, where amplifications of oncogenes and deletions of tumor suppressor genes are major steps in the "multi-hit" process of tumorigenesis. Genome-wide molecular biological analyses, such as loss of heterozygosity (LOH) profiling and comparative genomic hybridization (CGH) have significantly enhanced our ability to detect chromosomal aberrations in cancer cells and assess their role in tumorigenesis. The recent introduction of high-density oligonucleotide arrays for measuring single nucleotide polymorphisms (SNP) has sparked a new wave of high-resolution genetic mapping studies, including LOH and CGH applications on various cancer types. This review highlights recent progress on concurrent LOH and CGH analyses utilizing high density SNP arrays and their application in cancer research.

Genome, Human↗

Utilization review and containment for hospital utilization: some implications of providing care in the "most appropriate setting".

The study examines the potential for savings in the use of hospital resources if utilization review policies succeed in curtailing excessive use of hospital facilities. Excessive use is defined as the utilization of hospital care when ambulatory care is medically feasible and acceptable. A utilization review policy would be expected to counteract the tendency to substitute inpatient for outpatient treatment by assuring that all patients with identical medical problems and demographic traits would be treated in an identical least cost setting regardless of their social and economic circumstances. It might, thus, ascertain that the use of hospital facilities would not be systematically affected by patients' non-medical or socioeconomic characteristics. Specifically, the study distinguishes between two types of utilization control policies, pre-admission certification and concurrent or continuing-stay review of hospital episodes, and asks how each can contain excessive utilization. It concludes that continuing-stay review is not likely to have any appreciable effect on shortening hospital episodes because the effects of nonmedical factors on extended stay are small and concentrated among patients whose diagnoses might not qualify them for hospitalization under a pre-admission screen. However, pre-admission certification has a considerable potential for containment of hospital utilization through the reduction in the number of admissions. Also, as a corollary, the study shows that utilization review policies should not be evaluated, as they often are, in terms of their effect on length-of-stay, but rather in terms of their effects on hospital admissions and case mix.

Analysis of Variance↗

A Retrospective Study of Maintenance Electroconvulsive Therapy in a University-Based Psychiatric Practice.

We reviewed the log book of our university-based electroconvulsive therapy (ECT) service for the years 1981 to 1987. We identified 10 patients treated with monthly maintenance electroconvulsive therapy (ECT-M). These 10 patients received 3% of the ECT treatments given in this 7 year period. The review of their charts suggests that ECT-M is generally reserved for patients who are older (i.e., over 60 years of age), suffering from delusional depression and/or depressive pseudodementia, and have a history of poor response or tolerance to medications but good response to ECT. The patients had fewer hospitalizations in the 18 months after initiating ECT-M than during the 18 months preceding ECT-M (mean of 3.1 vs. 0.3, respectively, p < 0.001). However, this apparent efficacy of ECT-M may be confounded by the concurrent use of medication. A review of the literature reveals only descriptive studies on ECT-M and shows that our data are congruent with these published studies. The relative value of maintenance ECT and its specificity remain unknown. Its apparent impact on hospitalization rates and safety warrant controlled trials.

Journal Article↗

A utilization review of digoxin assays: sampling patterns and use.

A review of digoxin assay utilization concurrent with patient hospitalization was conducted at the University of Texas Medical Branch. An interdepartmental committee of clinicians adapted audit criteria for the collection and use of digoxin assays. This included rational indications, correct performance (i.e., collection and processing of serum sample) and appropriate dose adjustment. The charts of all patients receiving digoxin were examined daily, whether or not the physician had ordered a drug assay. Contributory data were collected and analyzed, including serum electrolyte concentrations, arterial blood gases, renal function tests, vital signs, physician assessments, and other information relating to pertinent and concomitant diseases or drug therapy. The 2-month review included 104 hospital inpatients who received 245 evaluations. Only 38.4% of the evaluations were determined to be compliant with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 66%, 73% and 86%, respectively. In 108 cases (52%), the physicians provided inadequate instructions in their request for the digoxin assay to insure proper collection time by the phlebotomist. Approximately 94% of all assay results were verbally communicated to the physician or returned to the patients' charts for use in patient management within a minimum of 24 hours. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used digoxin assays were estimated to exceed $100,900 annually. The audit was used to demonstrate the need for changes in hospital procedures and house staff training. A collaborative pharmacokinetics service was organized with reimbursement accomplished through the physician billing charge.

Digoxin↗

Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma. A case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm.

Thymoma is associated with benign and neoplastic diseases. The authors report the concurrence of invasive thymoma and T-lymphoblastic leukemia/lymphoma in a 95-year-old man. The hematologic malignancy was suspected terminally, whereas the thymoma was discovered at necropsy. The lymphoblastic leukemia/lymphoma had a clonally rearranged T-cell receptor beta-chain gene and a mature thymocyte immunophenotype. No retroviral gene sequences (human immunodeficiency virus 1 and 2, and human T-cell leukemia virus 1 and 2) were identified by polymerase chain reaction and hybridization analysis. The association of thymoma with hematologic neoplasm is reviewed.

Abdominal Neoplasms↗

Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients.

PURPOSE: To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group. RESULTS: Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis. CONCLUSIONS: Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.

Adenocarcinoma↗