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P Warde

Publications and source records attributed to P Warde.

At least 37 records · Page 2Linked to original sources
PubMed2001

Outcome of curative management of malignant tumours of the parotid gland.

PURPOSE: The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed. MATERIALS AND METHODS: A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour. RESULTS: All patients were initially managed with a parotidectomy, and postoperative x-ray radiation therapy (XRT) was administered to 159 patients. The actuarial 5-year cause-specific survival and locoregional control rates were 76% and 81%, respectively. The survival and locoregional control rates for patients treated with surgery alone versus surgery plus postoperative XRT were not statistically different. A multiple regression analysis identified only age and tumour category to be independently significant prognostic factors for both survival and locoregional control. CONCLUSION: We would recommend that patients with malignant parotid gland tumours be managed with parotidectomy, followed by postoperative XRT for tumours with residual disease, aggressive histology, and/or positive lymph nodes.

Adolescent↗
PubMed2001

Controversies in prostate cancer radiotherapy: consensus development.

The GU Radiation Oncologists of Canada (GUROC) had a consensus meeting in November 2000 to discuss and develop consensus on four controversial areas: risk assessment of localized prostate cancer, conformal radiotherapy, role of brachytherapy in prostate cancer and combined hormonal therapy and radiotherapy for prostate cancer. The meeting was a success and resulted in consensus being achieved on a number of areas. The group agreed on three risk groupings: low risk, intermediate risk and high risk localized prostate cancer based on clinical stage, Gleason score and PSA level. The participants agreed that based on available toxicity data from randomized controlled trials, conformal treatment techniques should be offered to patients receiving prostatic radiotherapy. Consensus was reached on the role of dose escalation in each of the three risk groups and is summarized in the article. At present there is insufficient evidence from randomized clinical trials to recommend the use of brachytherapy over current other standard therapy (radical prostatectomy or external beam radiotherapy). Non randomized published studies show promising short and intermediate term results. Where ever possible patients should be approached about participation in ongoing RCT's evaluating brachytherapy versus current other standard therapy. Outside a clinical trial the participants felt permanent seed implants should be considered an acceptable treatment option for appropriate patients with low risk prostate cancer. Based on randomized controlled trials the group agreed that patients with high risk disease should be treated with prolonged (up to 2-3 years) adjuvant hormonal therapy. Part of this hormonal treatment may be given in a neoadjuvant fashion. The group agreed that adjuvant hormones should not be routinely used in low and intermediate risk patients. Neoadjuvant hormones have been demonstrated to improve outcome in patients with bulky tumors. The role of neoadjuvant hormones in other patients with intermediate and low risk prostate cancer is unclear and will be clarified with the publication of recently completed studies. The consensus meeting strongly endorsed continued accrual to current studies investigating clinically relevant questions.

Antineoplastic Agents, Hormonal↗
PubMed2000

A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer.

One of the major side effects of radical radiation therapy for head and neck malignancies is xerostomia, or dryness of the mouth. There is no clearly effective treatment for this condition, but we have observed that patients in our practice believe that their symptoms improve significantly when using two "over-the-counter" oral comfort products - Biotene (toothpaste, mouthwash and chewing gum) and Oralbalance gel. We decided to study these agents in a formal phase II study to evaluate their usefulness in patients with postirradiation xerostomia. Twenty-eight patients with post-irradiation xerostomia were entered on the study. All had biopsy-proven carcinoma of the nasopharynx, oropharynx, oral cavity, hypopharynx or larynx, and had received primary radiotherapy with curative intent (> or =50 Gy in 20 fractions) more than 4 months before study entry. More than 75% of both parotid glands were included in the primary radiation field. There was no clinical evidence of recurrent disease. Patients were provided with a 2-month supply of Biotene mouthwash, toothpaste, chewing gum and Oralbalance gel. Response was evaluated 1 and 2 months after study entry using a patient-completed visual analogue scale to assess the severity of xerostomia and its effects on quality of life. For analysis, the scored baseline was subtracted from the later scores to assess change. Patients with an increase of 10 mm from their baseline score on the visual analogue scale were classified as having responded to the treatment intervention, and those with an increase of > or =25 mm from their baseline score were classified as having experienced a major improvement in their symptoms. After 2 months of treatment, 15 patients (54%) reported an improvement in intraoral dryness and 10 of these patients (36%) reported a major improvement. Similar proportions of patients (46% some improvement, 25% major improvement) reported an improvement in their ability to eat normally. Seventeen patients (61%) reported an improvement in oral discomfort, and 12 of these (43%) had a major improvement in their symptoms. The results of this study suggest that the use of Biotene (mouthwash, toothpaste and chewing gum) and Oralbalance gel can improve many of the symptoms of radiation-induced xerostomia. A placebo effect could account for many of the observed improvements in symptoms, and in order to assess the role of these agents in the management of patients with postirradiation xerostomia a randomised phase III study is needed.

Administration, Oral↗
PubMed2000

Carcinoma of the maxillary antrum: a retrospective analysis of 110 cases.

BACKGROUND AND PURPOSE: Cancer of the maxillary antrum is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with carcinoma of the maxillary antrum managed at a single institution. MATERIALS AND METHODS: A retrospective analysis of 110 cases of carcinoma of the maxillary antrum managed with curative intent during the time period 1976-1993 was performed. There were 33 females and 77 males; the median age was 64 years (range 38-89). The median follow-up time was 4 years (range from 2 months to 17 years). The majority of patients presented with locally advanced disease (78 T4 tumours); nodal involvement was observed in 17/110 cases. Histologic subtypes included in the analysis were limited to squamous cell carcinoma (95 cases) and undifferentiated carcinoma (15 cases). Patients were managed with either primary radiation therapy with surgery reserved for salvage (83/110) or with a planned combined approach with surgery and either pre or postoperative radiation (27/110). RESULTS: The actuarial 5-year cause-specific survival rate was 43%. The 5-year local control rate was 42%. Of 63 patients with local failure, 25 underwent salvage surgery with a subsequent 5-year cause-specific survival of 31%. Multiple regression analysis of patient, disease and treatment related variables identified local disease extent and nodal disease at presentation as the only variables independently associated with cause-specific survival. CONCLUSIONS: This analysis indicates that survival from carcinoma of the maxillary antrum is poor with outcome strongly related to local disease extent. The best treatment strategy for this disease remains undefined. Salvage surgery can result in prolonged survival in selected patients experiencing local failure.

Adult↗
PubMed2000

Impact of noninvasive imaging on increased incidental detection of renal cell carcinoma.

OBJECTIVE: To determine the impact of non-invasive imaging, specifically ultrasound imaging and computed tomography, on the incidental detection of renal cell carcinoma during two consecutive time periods, one prior and one subsequent to the acquisition of imaging equipment. METHODS: All located patient charts (83% of 207) of renal cell carcinoma cases (n = 172) were reviewed, and categorized by presentation method as 'incidental' or 'nonincidental' cases, based on defined criteria. Clinical information was recorded, cases were staged, and survival estimates were calculated. RESULTS: More than a third of the 172 cases were categorized as incidentally detected, most of which (82.5%) were detected during the latter time period. Either ultrasound or CT imaging was credited with detecting over 80% of the incidentally detected tumors. CONCLUSION: Ultrasound and CT imaging have contributed to the incidental detection of renal cell carcinomas during the two time periods. Stage significantly predicted survival (p<0.001) in a Cox proportional hazard model that also controlled for presentation, sex, and age.

Carcinoma, Renal Cell↗
PubMed2000

Long term outcome and cost in the management of stage I testicular seminoma.

PURPOSE: To validate the use of surveillance as an alternative to adjuvant RT in clinical stage I seminoma, we analyzed our experience with the two approaches in terms of long term outcome and cost. PATIENTS AND METHODS: Between January 1981 and December 1994, 471 patients with stage I testicular seminoma were treated at our institution. Of these, 245 patients received post-operative RT (25 Gy) to the retroperitoneal lymph nodes, and 226 have been managed with surveillance following orchidectomy. Two patients were included in this series twice; both had RT previously for seminoma, were placed on surveillance for a contralateral seminoma and were analyzed for outcome of both primary tumors. The costs associated with both approaches were estimated in 1994 Canadian dollars (C$). RESULTS: With a median follow-up of 7.7 years in the surveillance patients, and 9.7 years in the adjuvant RT cohort, the 5 year actuarial survival for all patients was 97% and the cause-specific survival (CSS) was 99.8%. Of the 226 patients on surveillance 37 patients have relapsed to date; five of those developed a second relapse. One patient has died of disease. Of the 245 patients treated with adjuvant RT, 14 patients have relapsed and none had a second relapse. The CSS was 100%. Thirteen patients on surveillance (5.7%) and 10 patients treated with post-operative RT (4.1%) have received chemotherapy as part of their management. One hundred and eighty-nine patients on surveillance have received no post-orchidectomy treatment to date. Surveillance was more expensive with an average additional cost per patient per year of Can$2620 over 10 years. CONCLUSIONS: Both adjuvant RT and surveillance give excellent results in stage I seminoma. The documented increased risk of second malignant tumors following RT must be taken into account when considering the additional cost of surveillance. The routine use of post-operative RT in stage I seminoma should be reconsidered and a surveillance program offered to all patients as an alternative management option.

Actuarial Analysis↗
PubMed1999

Management of testicular seminoma.

Testicular seminoma is highly curable with currently available treatments. Today, there is good evidence that patients with Stage I disease can be treated equally well with either immediate adjuvant para-aortic and ipsilateral pelvic radiotherapy or close surveillance with treatment at the time of relapse. The decision as to which of these management strategies is adopted in an individual case is a complex function of physician preference, and the emotional, social, and economic circumstances of the patient. Ongoing research in Stage I seminoma is focused at reducing the side-effects of treatment either by modifying the radiation treatment plan or by using adjuvant chemotherapy in lieu of radiation. Stage II patients with small bulk retroperitoneal lymphadenopathy have a high probability of long-term disease control with radiotherapy. Patients with bulky Stage II disease or Stage III disease should be treated with cisplatin-based chemotherapy.

Analysis of Variance↗
PubMed1999

Neoadjuvant hormonal therapy in carcinoma of the prostate.

The rising incidence of and mortality from prostate cancer has generated great interest in improving the results of current methods of treatment. It is well-established that large tumour volumes and positive surgical margins are correlated with higher rates of local failure and distant metastasis. Significant decreases in both tumour volume and the rates of positive surgical margins are seen with NHT. Follow-up data from one randomized trial of hormonal therapy before RT have shown significantly improved disease-free survival, but so far there has been no benefit in overall survival. However, the addition of adjuvant hormonal therapy has been reported to improve survival. The results suggest that neoadjuvant and adjuvant hormonal therapy may be a viable option in men with locally advanced prostate cancer in whom cure is probably impossible, but disease progression can potentially be slowed. What remains to be determined is whether hormonal therapy alone can produce the same results. For younger men with clinically localized prostate cancer, radical prostatectomy is increasingly the treatment of choice. Prospective randomized trials of NHT have produced impressive statistics for decreasing the incidence of positive surgical margins, but the potential to down-stage tumours remains controversial. Follow-up serum PSA measurements have thus far shown no benefit from neoadjuvant therapy. The possibility that patients who fail biochemically, whether they are from the pretreated or control group, may simply represent a subgroup with aggressive tumours that may not respond to androgen withdrawal, has yet to be proved. As more follow-up data are analysed within the next several years, there must be a clear survival advantage if NHT is to be offered as a treatment option. Despite the potential of neoadjuvant therapy, the use of androgen withdrawal before definitive surgical treatment should be limited to clinical trials until a clearer picture emerges. Some may argue that although there is no evidence of a true advantage for NHT, neither is there evidence of harm. However, it must be recognized that androgen withdrawal therapy has side-effects and adds significantly to the overall cost of treatment. Furthermore, NHT delays definitive treatment; clearly, this can be a source of anxiety for the patient and the impact on survival is unknown. Currently, the rates of pathologically organ-confined disease are high in some subsets of patients (e.g. low-stage, low-grade and low PSA) so that NHT is unlikely to have great additional benefit. Although the influence of hormones on prostate growth has been known for many decades, we are only now elucidating the biological mechanisms of hormonal therapy. Although androgen ablation therapy has been used in men with metastatic prostate cancer for more than 50 years, further research at the cellular and molecular level is essential if we are to refine treatment modalities for both localized and advanced disease. Furthermore, until we have more follow-up data from randomized clinical trials of NHT, it cannot be considered part of the standard treatment for carcinoma of the prostate. There are still too many unknown factors; only time will tell if the initial promise of NHT will be fulfilled.

Antineoplastic Agents, Hormonal↗
PubMed1998

Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.

PURPOSE: To describe the outcome of patients with carcinoma of the ethmoid sinus managed with a policy of primary radiation therapy with surgery for salvage of persistent or progressive disease. METHODS AND MATERIALS: A retrospective chart review was undertaken of 29 patients with the diagnosis of carcinoma of the ethmoid complex who underwent treatment in the period between January 1976 and December 1994 at the Princess Margaret Hospital. Analysis was confined to those patients with epithelial invasive histology (squamous carcinoma, adenocarcinoma, or undifferentiated carcinoma) managed with curative intent with primary radiation therapy. The median patient age was 62, with a median follow-up time of 4 years. Staging was assigned according to a modification of the UICC 1997 system with 19 (66%) of patients presenting with T4 category tumors. The most common radiation dose regimes were 60 Gy in 30 daily fractions over 6 weeks, or 50 Gy in 20 daily fractions over 4 weeks. Outcome was analyzed with respect to overall survival, cause-specific survival, and local progression-free survival. The influence of a variety of clinical and therapeutic factors on outcome is discussed, the patterns of disease failure are described, and the rationale for this treatment approach is outlined. RESULTS: The 5-year rates of overall survival, cause-specific survival, and local progression-free survival were 39%, 58%, and 41%, respectively. A total of 18 of 29 patients died during the period of review. Of these, 12 deaths were due to ethmoid cancer, one was due to a second primary lung cancer, and five were attributed to nononcologic causes. No patients died due to treatment-related toxicity. Increasing T category predicted for worse outcome on univariate analysis. Local progression was the major cause of treatment failure and was documented in 15 of 29 patients treated (52%). Six patients were offered salvage surgery for local progression, of whom two remained disease free at 15 and 17 months follow-up. CONCLUSIONS: Outcome of patients with ethmoid cancer managed with primary radiation therapy with surgery for salvage is comparable to that achieved with planned combined modality approaches. Nevertheless, outcome remains poor and is dependent on the local extent of tumor, with 40-50% of patients eventually succumbing to disease.

Adenocarcinoma↗
PubMed1998

T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control.

PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However, in many settings, the adverse effect of a low Hb may be related to more advanced disease. The purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localized cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63; 657 males, 78 females) with T1/T2 glottic cancer were treated with radiation therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks (97% of patients). Factors studied for prognostic importance for local failure included pretreatment Hb, age, sex, T category, anterior commissure involvement, subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131 patients have locally relapsed for an actuarial 5-year relapse-free rate of 81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin level was 14.8 g/dl and was similar in all prognostic categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb predicted for local failure after RT. The hazard ratio (HR) for relapse was calculated for various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl was 1.8 (95% confidence interval 1.2-2.5). Previously established factors, including gender, T category, subglottic extension, as well as tumor bulk, were also prognostically important for local control. CONCLUSIONS: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with RT. The underlying biology of this observation needs to be explored, and using this information, it may be possible to develop strategies to improve treatment outcome.

Carcinoma, Squamous Cell↗
PubMed1998

Surveillance for stage I testicular seminoma. Is it a good option?

Postorchidectomy treatment options in patients with stage I seminoma include surveillance (reserving treatment for patients who relapse), adjuvant radiation therapy (RT), and adjuvant chemotherapy. Adjuvant retroperitoneal RT remains the treatment of choice in most centers; however, the success of surveillance in stage I nonseminomatous germ cell testis tumors, the establishment of curative chemotherapy for advanced disease, and the improvements in CT have led to re-examination of the standard treatment approach. The available data from the surveillance and adjuvant RT series suggest that almost 100% of patients with stage I testicular seminoma are cured, whichever approach is chosen. This article presents an overview of the available information on all treatment options, the pros and cons of each approach, and indications for where surveillance fits into the armamentarium of clinicians dealing with this disease.

Combined Modality Therapy↗
PubMed1998

Magnetic resonance imaging (MRI) for localization of the prostatic apex: comparison to computed tomography (CT) and urethrography.

BACKGROUND AND PURPOSE: It is necessary to include the entire prostate in the high dose treatment volume when planning radical radiation for patients with prostate cancer. We prospectively compared magnetic resonance imaging (MRI) to computed tomography (CT) and urethrography as means of localizing the prostatic apex. MATERIALS AND METHODS: Thirty patients with clinically localized prostate cancer had a sagittal T2-weighted MRI scan and a conventional axial CT scan performed in the treatment position prior to the start of radiotherapy. Twenty of these patients had a static retrograde urethrogram performed at simulation. The position of the MRI and CT apices were localized independently by two radiation oncologists. In addition, the MRI apex was localized independently by a diagnostic radiologist. The urethrogram apex, defined as the tip of the urethral contrast cone, was easily identified and was therefore localized by only one observer. RESULTS: There was good interobserver agreement in the position of the MRI apex. Interobserver agreement was significantly better with MRI than with CT. There were no systematic differences in the position of the MRI and CT apices. However, the MRI apex was located significantly above and behind the urethrogram apex. There was poor correlation between MRI and CT and between MRI and urethrogram in the height of the apex above the ischial tuberosities. There was 83% agreement between MRI and CT and 80% agreement between MRI and urethrogram in the identification of patients with a low-lying apex. The apex, as determined by MRI, was <2 cm above the ischial tuberosities and therefore potentially under-treated in 17% of the patients. CONCLUSIONS: MRI is superior to CT and urethrography for localization of the prostatic apex. All patients undergoing radiotherapy for prostate cancer should have localization of the apex using MRI or a technique of equal precision to assure adequate dose delivery to the entire prostate and to minimize the unnecessary irradiation of normal tissues.

Adenocarcinoma↗
PubMed1998

Management of stage II seminoma.

PURPOSE: To assess the results of treatment, patterns of failure, and prognostic factors for relapse in a contemporary cohort of patients with stage II seminoma. MATERIALS AND METHODS: From January 1981 and December 1993, 99 patients (median age, 35 years) with stage II seminoma (IIA, 41; IIB, 28; IIC, 24; IID, six) were managed at our institution. Eighty were treated with radiation therapy (RT) and 19 with chemotherapy (ChT). RESULTS: With a median follow-up of 6.7 years, the five-year overall actuarial survival was 94%, the 5-year cause-specific survival was 94%, and the 5-year relapse-free rate was 83%. Sixteen (20%) of the 80 patients treated with RT relapsed (median time to relapse, 9 months). Relapse occurred outside the irradiated area in all but two patients. Distant relapse sites included the supraclavicular fossa, bone (four patients, three with spinal cord compression), and lung/mediastinum. All 19 patients treated primarily with ChT achieved disease control and none has relapsed. The relapse rate at 5 years for patients with stage IIA to IIB was 11% (seven of 64), and 56% (nine of 16) for those with stage IIC to IID disease (P < .0001). No patient with IIC or IID disease treated with ChT relapsed as compared with 56% of patients treated with RT (0 of 14 v nine of 16, P = .002). CONCLUSION: Radiation therapy is highly effective in patients with stage IIA or IIB seminoma (89% were relapse free). In stage IIC or IID disease, although local control with RT is excellent, a 50% risk of distant relapse is unacceptable, and not all patients who relapse can be salvaged. Chemotherapy should clearly be the primary treatment in patients with stage IIC or IID seminoma.

Adult↗
PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗
PubMed1997

Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin.

BACKGROUND: We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer. METHODS: From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin. RESULTS: Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001). CONCLUSIONS: Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer.

Adenocarcinoma↗