Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma.

BACKGROUND: Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS: Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS: Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION: In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.

Treating advanced cancer of the gastro-oesophageal junction (GOJ) poses a challenge given its location in the distal oesophagus and proximal stomach, and whether it should be treated as oesophageal or gastric cancer. Given the indistinct location, it is unclear whether GOJ cancer should be treated with neoadjuvant chemoradiation, which is the treatment of choice for advanced oesophageal cancers, or perioperative chemotherapy, which is the treatment of choice for advanced gastric cancers. Few studies have addressed treatment options specifically for GOJ cancers. This study investigated whether there was a difference in survival between patients with GOJ cancer who were treated with chemoradiation versus chemotherapy.

A qualitative study exploring factors influencing clinical decision-making for influenza-like illness in Solapur city, Maharashtra, India.

The co-existence of different types of medical systems (medical pluralism) is a typical feature of India's healthcare system. For conditions such as influenza-like illness (ILI), where non-specific disease signs/symptoms exist, clinical reasoning in the context of medical pluralism becomes crucial. Recognising this need, we undertook a qualitative study, which explored factors underpinning clinical decisions on diagnosis and management of ILI. The study involved semi-structured interviews including clinical vignettes with 20 healthcare practitioners (working within allopathy, homeopathy and Ayurveda) working in the private healthcare sector in Solapur city, India. An inquiry was conducted into criteria influencing the diagnosis, treatment, referral to specialist care and role of treatment guidelines for ILI. Thematic analysis was used to identify aspects relating to ILI diagnosis, treatment and referral. The diagnosis of influenza was based largely on clinical symptoms suggestive of influenza in the absence of other diagnoses. Referral for laboratory tests was only initiated if illness did not resolve, generally after 2-3 consultations. Antibiotics were often prescribed for persistent illness, with antivirals rarely considered. Some differences between practitioners from different medical systems were observed in relation to treatment and referral in case of persistent illness. A combination of analytical and intuitive clinical reasoning was used by the participants and clinical decisions were based on both social and clinical factors. Clinical decision-making was rarely a linear process and respondents felt that broad guidelines on influenza that allowed doctors to account for the sociocultural context within which they practised medicine would be helpful.

Nature of events and alcohol-related content in marketing materials at a university freshers' fair: a summative content analysis.

Introduction: The transition to university is a potentially influential time upon students' drinking behaviour. This study explored the nature of activities and alcohol-related content in marketing materials from student-led societies and local businesses provided to students, at a university freshers' fair in the UK. Methods: All marketing materials handed out at the fair were collected across the 5-day event in September 2015. Written and visual content was analysed using a summative qualitative content analysis. Results: Most student-led societies promoted social events they were hosting (n = 530), most of which took place in a drinking venue or referred to drinking (n = 335). Only four explicitly alcohol-free events were promoted. Student-led societies also promoted activities relating to their interest, e.g. sports training (n = 519), a small proportion of which had references to drinking and drinking venues (n = 54). Three societies provided promotional handouts from local bars or nightclubs. Local bars, pubs and nightclubs promoted events they hosted (n = 81) as well as alcoholic drink promotions (n = 79) and alcohol branded advertising (n = 22), albeit infrequently for the latter. Conclusions: In the first week of university, students are exposed to alcohol-related events, promotions and advertising, which may act as an incentive to participate in drinking.

Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.

This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease.

Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy.

Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rates of pathological complete response. A pathological complete response is recognized to be an important predictor of improved survival, to the extent that observation rather than surgery is advocated by some in patients with presumed pathological complete response based on their clinical response. The goal of this study was to look at the ability of clinical variables to predict pathological complete response after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients with locally advanced esophageal squamous cell carcinoma who underwent chemoradiotherapy followed by surgery and compared those with pathological complete response to patients with residual disease. Between January 1996 and December 2010, 116 patients met inclusion criteria. Fifty-six percent of patients had a pathological complete response and a median survival of 128.1 months versus 28.4 months in patients with residual disease. When compared with patients with residual disease, patients with a pathological complete response had a lower post-neoadjuvant positron emission tomography (PET) maximum standardized uptake value (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post-chemoradiotherapy computed tomography and a higher rate of normal appearing post-chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of these characteristics alone was able to correctly identify patients with a pathological complete response, and none has significant specificity. Although the rate of pathological complete response after chemoradiotherapy is high in patients with esophageal squamous cell carcinoma, the ability of identifying patients with pathological complete response is limited. A reduction of the PET SUVmax by >70%, a normal appearing endoscopic examination, and no residual disease on biopsy all were seen in >65% of the patients with a pathological complete response. Even if these findings were unable to confirm the absence of residual disease in the primary tumor, they can help guide expectant management in high-risk patients.

The impact of colorectal cancer and self-efficacy beliefs on work ability and employment status: a longitudinal study.

We examined how colorectal cancer patients' treatment and symptom management impacted perceptions of work ability and subsequent work decisions. Fifty patients completed questionnaires at baseline (post-surgery/pretreatment), 3 months and 6 months. Questionnaires assessed fatigue, depression, quality-of-life (QoL), cancer self-efficacy, job self-efficacy (JSE) and work ability. Factors related to perceived work ability were occupation (ß= 0.31, P= 0.0005) and QoL (ß= 0.42, P= 0.01) at baseline, treatment type (ß=-0.19, P= 0.05) at 3 months, and JSE at 3 months (ß= 0.57, P= 0.0005) and 6 months (ß= 0.50, P= 0.006). Factors related to being on sick leave were lower levels of JSE (OR = 2.20, 95% CI: 1.17-4.13) at baseline and being employed in a manual occupation (OR = 0.03, 95% CI: 0.00-0.86), and perceived work ability (OR = 3.05, 95% CI: 1.00-12.80) at 6 months. Along with self-assessed work ability at baseline (ß= 0.67, P= 0.0005), receiving chemotherapy or a combination of treatments (ß=-0.24, P= 0.05) were the strongest predictors of poorer perceptions of follow-up work ability. Self-efficacy beliefs may add to understanding and should be considered in future research.

Effectiveness and acceptability of face-to-face, blended and e-learning: a randomised trial of orthodontic undergraduates.

AIM: This study compared e-learning (EL), face-to-face learning (F2FL) and blended learning (BL) with respect to their effectiveness and student attitudes towards them. It also evaluated the effect of the order in which the components (EL and F2FL) of blended learning are delivered. DESIGN: This was a prospective cluster randomised trial comparing four parallel groups. METHOD: Eight groups of fourth year dental undergraduate students were randomly allocated to one of four intervention groups: EL, F2FL, BL1 or BL2. These four groups were assessed for their baseline comparability of knowledge and skills. Each then received the same cephalometric tutorial but delivered by the allocated mode of learning. Effectiveness was immediately assessed with a MCQ which measured short-term recall of knowledge. Student attitudes were evaluated with a questionnaire followed by a focus group discussion. RESULTS: Ninety (57%) students completed the study. Pearson's chi-square test found no statistically significant difference between F2FL and BL; EL alone was less effective (P<0.05) for four MCQ questions but with no difference for the remaining six questions. Overall students were positive towards each learning modality, but a one-way analysis of variance found BL was the most and F2FL was the least accepted (P=0.002). EL was significantly (P=0.028) less preferred. The order of the components in BL had no significant effects. CONCLUSION: These results suggest that BL is more likely than either F2FL or EL alone, to be both effective and accepted when delivering cephalometric education to undergraduates.

Identification of microRNAs that promote erlotinib resistance in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths, demanding improvement in current treatment modalities to reduce the mortality rates. Lung cancer is divided into two major classes with non-small cell lung cancer representing ~84% of lung cancer cases. One strategy widely used to treat non-small cell lung cancer patients includes targeting the epidermal growth factor receptor (EGFR) using EGFR-inhibitors, such as erlotinib, gefitinib, and afatinib. However, most patients develop resistance to EGFR-inhibitors within a year post-treatment. Although some mechanisms that drive resistance to EGFR-inhibitors have been identified, there are many cases in which the mechanisms are unknown. Thus, in this study, we examined the role of microRNAs in driving EGFR-inhibitor resistance. As mediators of critical pro-growth pathways, microRNAs are severely dysregulated in multiple diseases, including non-small cell lung cancer where microRNA dysregulation also contributes to drug resistance. In this work, through screening of 2019 mature microRNAs, multiple microRNAs were identified that drive EGFR-inhibitor resistance in non-small cell lung cancer cell lines, including miR-432-5p.

The role of communication and support in return to work following cancer-related absence.

OBJECTIVE: Many cancer survivors experience difficulties returning to work. However, there have been relatively few attempts to understand why problems with employer support and work adjustment occur. This paper aims to extend previous work in two ways: first, through exploring the way in which communication and support at work effect cancer survivors on their return to work and during the post-return period; and second, by drawing on a research sample working in the United Kingdom. METHODS: In all, 26 cancer survivors took part in a semi-structured telephone interview. Interviews were transcribed and analysed using thematic analysis. RESULTS: The analysis revealed three key findings. First, the central role of communication and support from (and between) occupational health, line managers, and colleagues was highlighted. Second, two discrete processes or periods of return to work were identified: the experience of return to work during the initial period of return and the experiences of post-return to work. Third, during the post-return period, the importance of the delayed impact of cancer on the ability to work, the lack of follow-up and monitoring, and the wear-off effect of empathy and support were highlighted as contributing to return-to-work difficulties. CONCLUSIONS: This qualitative study highlights the importance of communication within the workplace with regard to the return-to-work process and the need to provide better support and guidance to cancer survivors, line managers and colleagues. Research is required in delineating how employers without occupational health or human resources support manage the return-to-work process.

Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

BACKGROUND: Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined. PATIENTS AND METHODS: We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC. RESULTS: Twenty-five patients were identified, with complete records available for 22. Eighty-two percent were male, 82% had pure SCC histology and 86% of tumors were in the lower esophagus or GE junction. On the basis of the Veterans' Administration Lung Study Group criteria, 14 patients (64%) presented with limited disease (LD). Median survival was 19.8 months (range, 1.5 months to 11.2+ years); for LD patients, 22.3 months (range, 6 months to 11.2+ years); for extensive disease (ED) patients, 8.5 months (range, 1.5 months to 2.2 years, P = 0.02). With a median follow-up of 38 months, six patients (27%) are alive, one with ED and five with LD. Two LD patients are alive and free of disease for >5 years. Four of the five LD patients who are long-term survivors received induction chemotherapy followed by chemoradiotherapy without surgery. CONCLUSIONS: Our data indicate that patients with LD esophageal SCC treated with induction chemotherapy followed by consolidative chemoradiation can achieve long-term survival. The contribution of surgery remains unclear.

Predictors of return to work following carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an important part of secondary prevention in selected patients following a transient ischaemic attack or stroke. A key marker of success, return to work following surgery, was assessed in a retrospective cohort study. METHODS: Patients from the UK aged less than 65 years at operation were sent a questionnaire concerning return to work after CEA. Data were analysed using univariable tests and logistic regression. RESULTS: Some 174 (64.4 per cent) of 270 patients responded; their median age was 60 (range 35-64) years and 124 were men. Seventy-five per cent of respondents employed preoperatively returned to work following CEA. Newly retiring patients were older (62 versus 58 years; P < 0.001). Univariable analysis confirmed that age and preoperative stroke influenced return to work. The adjusted odds ratio for patients with versus without a preoperative stroke was 0.46 (95 per cent confidence interval 0.22 to 0.97) (P = 0.040). Median convalescence was 4 weeks, but was shorter in the self-employed (P = 0.039) and prolonged in patients with symptomatic cardiovascular disease (P = 0.023) and those who required postoperative critical care (P = 0.039). CONCLUSION: Return to work following CEA was influenced by age and preoperative stroke.

Microwave Ablation in the Management of Colorectal Cancer Pulmonary Metastases.

PURPOSE: To review outcomes following microwave ablation (MWA) of colorectal cancer pulmonary metastases and assess predictors of oncologic outcomes. METHODS: Technical success, primary and secondary technique efficacy rates were evaluated for 50 patients with 90 colorectal cancer pulmonary metastases at immediate, 4-8 weeks post-MWA and subsequent follow-up CT and/or 18F-FDG PET/CT. Local tumor progression (LTP) rate, LTP-free survival (LTPFS), cancer-specific and overall survivals were assessed. Complications were recorded according to SIR classification. RESULTS: Median follow-up was 25.6 months. Median tumor size was 1 cm (0.3-3.2 cm). Technical success, primary and secondary technique efficacy rates were 99, 90 and 92%, respectively. LTP rate was 10%. One-, 2- and 3-year LTPFS were: 93, 86 and 86%, respectively, with median LTPFS not reached. Median overall survival was 58.6 months, and median cancer-specific survival (CSS) was not reached. One-, 2- and 3-year overall and CSS were 94% and 98, 82 and 90%, 61 and 70%, respectively. On univariate analysis, minimal ablation margin (p < 0.001) and tumor size (p = 0.001) predicted LTPFS, with no LTP for minimal margin ≥ 5 mm and/or tumor size < 1 cm. Pleural-based metastases were associated with increased LTP risk (p = 0.002, SHR = 7.7). Pre-MWA CEA level > 10 ng/ml (p = 0.046) and ≥ 3 prior chemotherapy lines predicted decreased CSS (p = 0.02). There was no 90-day death. Major complications rate was 13%. CONCLUSIONS: MWA with minimal ablation margin ≥ 5 mm is essential for local control of colorectal cancer pulmonary metastases. Pleural-based metastases and larger tumor size were associated with higher risk of LTP. CEA level and pre-MWA chemotherapy impacted CSS.

c-myc and c-myb oncoproteins during induced maturation of myeloid and erythroid human leukemic cell lines.

c-myc and c-myb mRNAs have been found to be tightly regulated during hemopoietic differentiation. We have studied nuclear c-myc and c-myb oncoproteins through the cell cycle, during macrophage, granulocyte, erythroid, and megakaryocytic differentiation of KG1, HL60, and HEL cells. p62c-myc and p75c-myb content of propidium iodide-stained nuclei was quantitated by flow cytometry using fluoresceinated antibodies CT14-G4 and MB4.3, respectively. In uninduced cells p62c-myc content is highest in HL60, followed by HEL, then KG1, while p75c-myb is highest in HEL, followed by HL60 and KG1. All lines showed a less than 2-fold increment in both oncoproteins over the cell cycle. Macrophage induction of KG1 and HL60 resulted in early increase in both oncoproteins, followed by a decline to less than starting values by 48 h, concurrent with a reduction of S phase cells and the appearance of adherent alpha-naphthyl acetate esterase-positive cells. p62c-myc changes were more pronounced in HL60 and p75c-myb changes in KG1. Different patterns of oncoprotein expression were found when different inducing agents were used for granulocyte differentiation of HL60. Under all conditions, however, both oncoproteins declined to basal levels before granulocyte maturity. Hemin-induced erythroid differentiation of HEL to hemoglobin-containing cells resulted in biphasic p62c-myc and p75c-myb kinetics. In contrast, dimethyl sulfoxide-induced megakaryocytic differentiation of HEL was accompanied by an early and steady decline in both oncoproteins. Despite considerable reduction in oncoprotein levels, HEL cells were still actively cycling at 120 h. It appears that c-myc and c-myb proteins decline with differentiation, well before proliferation ceases in some lineages. The kinetics of the decline differ between the two oncogenes and vary with the lineage induced and the nature of the inducing agent used. The cell cycle distribution of the oncoproteins does not change during maturation. These data suggest disparate roles for c-myc versus c-myb during hemopoietic differentiation and the existence of multiple signal transduction pathways for down-regulation of these genes.

The treatment of extragonadal seminoma.

Primary extragonadal seminoma (EGS) is a rare tumor of young adults that often presents with bulky primary tumors and metastatic disease. Long-term survival is inadequate with conventional therapy consisting of radiotherapy with or without surgery. The charts of 21 patients with EGS treated initially either with conventional therapy (group I) or with multimodality therapy including initial chemotherapy with high doses of cisplatin followed by either radiotherapy or surgery or both (group II) were reviewed. Five of the ten patients in group I developed recurrent disease and four of them eventually died of disease. Only one of 11 patients in group II died of metastatic disease and the remaining patients are free of disease with 19+ to 46+ months of follow-up. Of the six patients from group II who underwent surgical resection of apparently residual disease after chemotherapy but prior to radiotherapy, five were found to have completely necrotic tumor and one had microscopic disease on histologic examination, proving the efficacy of chemotherapy. Combined modality therapy including initial chemotherapy containing high doses of cisplatin provided rapid reduction in tumor burden and the results appeared superior to treatment that did not include initial chemotherapy.

VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors.

One hundred sixty-six patients with germ-cell tumors (GCT) of the testis, retroperitoneum, and mediastinum were treated with cyclophosphamide, vinblastine, bleomycin, dactinomycin, and cisplatin (VAB-6), with and without maintenance chemotherapy. The overall complete response (CR) rate was 78%, 67% to chemotherapy alone, and 11% after chemotherapy and resection of viable residual cancer. The CR rate in all patients with seminoma was uniformly high, while the CR rate of patients with testicular nonseminomatous germ-cell tumors (79%) was superior to that of similar tumors of extragonadal origin (60%). The overall relapse rate was 12%, and was greater in tumors of extragonadal origin (21%) than in those of testicular origin (11%). Three relapses occurred after 2 years. Maintenance chemotherapy did not prolong either relapse-free or total survival. Toxicity was tolerable, and there were no treatment deaths. No Raynaud's phenomena have occurred, with a minimum duration since start of therapy of 36 months. VAB-6 is an effective chemotherapy regimen in patients with GCT with no treatment-related deaths and a majority of patients requiring only 3 months of treatment.

Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum.

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum. PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P =.003) and more than one site resected during surgery (P =.06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P =.33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P =.09). CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.

Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer.

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m(2), and cisplatin 100 mg/m(2) were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m(2); the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1, 200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.

Palatal perforations: past and present. Two case reports and a literature review.

Syphilis and cocaine abuse are posing a growing public health problem on a global and national scale. Clinicians are increasingly likely to come across associated oral manifestations. We present two cases of palatal perforations caused by tertiary syphilis and cocaine abuse respectively. The literature review discusses issues specific to palatal perforations and those general to both conditions. The purpose of the report is to focus attention on syphilis and cocaine abuse as rising problems for the dental profession.