贲门失弛缓症并发食管癌临床及X线分析

目的：提高贲门失弛缓症并发食管瘤的早期临床X线诊断。材料与方法：21例贲门失弛缓症并发食管癌均经病理证实，作者回顾分析了其临床及X线表现。结果：21例贲门失弛缓症并发食管癌，占我院同期收治食管癌的0．078％，占失治贲门失弛症的1．59％。失弛症病史为8～28年。4例曾作手术治疗。X线检查失弛症重度14例，中度7例。癌位于胸食管上段5例，中下段16例，病变平均长度9cm。结论：贲门失弛缓症有可能因长期食物潴留引起食管炎症，促使食管鳞状上皮变性和癌变。早期手术治疗可缓解症状，但仍有术后并发癌变的病例。对病史长、年龄较大患者，应做详细的食管双对比造影，多轴摄片以及食管镜检查，以提高病变的早期检出率。     

Multiple carcinomas following therapy for Hodgkin disease.

A 52-year-old man developed synchronous squamous-cell carcinoma of the larynx and middle one-third of the esophagus following treatment of Hodgkin disease. This patient fell into the subgroup of patients treated by intensive radiation therapy followed by intensive chemotherapy. The link between the therapy and subsequent carcinoma is suggestive. Long-term follow-up care of patients with Hodgkin disease demands continuing evaluation of this possible complication.     

Hodgkin disease in monozygotic twins: A case report

Presented are the case histories of monozygotic male twins concordant for Hodgkin disease. This is believed to be the third such case report in the world literature. Its significance as it relates to the role of heredity in carcinogenesis is discussed.     

Vera Peters and the curability of Hodgkin disease

The middle of the 20th century hailed the realization that patients with Hodgkin disease could be cured. Through the groundbreaking work of Vera Peters, patients with a localized form of the disorder, previously thought to be incurable, were shown to be cured by extended-field radiotherapy. This important observation, although not immediately accepted, opened the minds of physicians to take more positive investigative and therapeutic approaches. Peters also introduced and championed the concept of tumour staging in Hodgkin disease and the use of prognostic factors in clinical decision-making. This novel approach led to high cure rates with radiotherapy in localized disease and provided a scientific basis for the subsequent use of chemotherapy in disseminated disease, resulting in a very high cure rate in patients with all stages of Hodgkin disease.     

Tumor associated macrophages in relapsed and refractory Hodgkin lymphoma

Background

Growing evidence demonstrates that an increased number of CD68 positive tumor-associated macrophages (TAM) is associated with decreased survival in patients with newly diagnosed classic Hodgkin lymphoma (HL). However, the impact of TAM in relapsed and refractory disease is unknown.

Design and methods

To investigate whether the presence of elevated CD68 retains its prognostic significance in the relapsed and refractory setting, we analyzed pre-salvage biopsy specimens of 81 patients with relapsed and refractory HL using a tissue microarray. Scoring of CD68 was based on the percentage of CD68 positive TAM compared to the total number of cells in representative areas. The final percent of CD68 positivity for each case was based on the average of cores available for examination.

Results

In a univariate analysis, we found that patients with elevated levels of CD68 positive TAM had inferior overall survival (OS) compared with patients who had lower CD68 levels. For patients undergoing autologous stem cell transplant after salvage treatment, elevated CD68 levels were predictive of both adverse OS and event free survival. However, after adjusting for other variables, increased CD68 positive TAM did not retain prognostic significance in a multivariate model.

Conclusions

In our dataset of primary refractory and relapsed Hodgkin lymphoma biopsy specimens, TAM infiltration is unable to definitively predict outcome. In order to validate these findings, TAM infiltration of relapsed and refractory specimens should be assessed prospectively and paired to initial Hodgkin lymphoma biopsies at diagnosis.     

Thymic hyperplasia associated with Hodgkin disease and thyrotoxicosis.

A 19-year-old woman had a residual gallium-sequestering mediastinal mass after treatment for Hodgkin disease. Coincidentally, she also had hyperthyroidism. The initial concern was that the mass was residual Hodgkin disease. Thymic hyperplasia has been described in association with both these conditions. The mass disappeared after treatment of her hyperthyroidism.     

Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma.

BACKGROUND: In the National Cancer Institute of Canada Clinical Trials Group/Eastern Cooperative Oncology Group HD.6 trial, progression-free survival was better in patients randomized to therapy that included radiation, compared to doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) alone. We now evaluate patterns of progression and subsequent outcomes of patients with progression. PATIENTS AND METHODS: After a median of 4.2 years, 33 patients have progressed. Two radiation oncologists determined whether sites of progression were confined within radiation fields. Freedom from second progression (FF2P) and freedom from second progression or death (FF2P/D) were compared. RESULTS: Reviewers agreed for the extended (kappa = 0.87) and involved field (kappa = 1.0) analyses. Progression after ABVD alone was more frequently confined within both the extended (20/23 vs. 3/10; P = 0.002) and involved fields (16/23 vs. 2/10; P = 0.02). There was no difference in FF2P between groups [5-year estimate 99% (radiation) versus 96% (ABVD alone)] [hazard ratio (HR) = 3.14, 95% confidence interval (CI) 0.63-15.6; P = 0.14]; the 5-year estimates of FF2P/D were 94% in each group (HR = 1.04, 95% CI 0.41-2.63; P = 0.93). CONCLUSION: Treatment that includes radiation reduces the risk of progressive Hodgkin lymphoma in sites that receive this therapy, but we are unable to detect differences in FF2P or FF2P/D.     

Successful treatment of non‐Hodgkin lymphoma associated immune thrombocytopenia with involved field radiotherapy

Immune thrombocytopenia complicates the course and impacts the outcome of non‐Hodgkin lymphoma (NHL‐ITP, non‐Hodgkin lymphoma–immune thrombocytopenic purpura). The response to corticosteroids and/or intravenous immune globulins is usually short lasting, but NHL‐ITP usually responds to anti‐lymphoma chemotherapy. It is not clear if this success is due to the elimination of the lymphomatous tissue or to the immunosuppressor/immunomodulator effect of chemotherapy. Myelosuppressive anti‐lymphoma chemotherapy carries the risk of severe thrombocytopenia that may not respond adequately to platelet transfusion support. We report on a patient with recurrent diffuse large B‐cell lymphoma that coincided with immune thrombocytopenia. Both diseases completely responded to involved field radiation therapy. This supports the hypothesis that at least in some cases of NHL‐ITP, the lymphomatous clone secretes the anti‐platelet antibodies. This supports the therapeutic decision making for these patients. Copyright © 2013 John Wiley & Sons, Ltd.     

ACHALASIA AND CARCINOMA OF THE ESOPHAGUS

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Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma

BACKGROUND: Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20-positive, good prognostic lymphoma in children. Patients with early-stage LPHL who underwent successful surgical lymph node resection alone have been reported. To clarify the optimum treatment strategy in children, European study groups were asked to report their experience of surgery alone used in the treatment of pediatric LPHL. METHODS: Data from 58 patients were collected by the French Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls, and the median age was 11 years (age range, 4-17 years). Fifty-four patients had stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA disease. RESULTS: With a median follow-up of 43 months (range, 2-202 months), the overall survival rate was 100%, and the progression-free survival (PFS) rate was 57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All seven patients who had residual disease after initial surgery developed recurrences (P = .003). Among 18 patients with stage IA LPHL who developed recurrent disease, 11 patients had local recurrences, and 7 patients recurred in stage IIA. One patient with stage IIIA disease presented with high-grade B-cell non-Hodgkin lymphoma at 10 years of follow-up. CONCLUSIONS: When complete resection was achieved, a substantial proportion of patients with surgically treated, early-stage LPHL experienced long-term remission and actually may have been cured.     

Recent Results on the Biology of Hodgkin and Reed-Sternberg Cells. I. Biopsy Material

The most recent sophisticated investigations have provided new and revealing, but also contradictory and controversial information on the biological nature and the cellular origin of Hodgkin and Reed-Sternberg cells (H-RS). Immunophenotypic analyses have shown variable phenotypic antigen expression; but, on balance the data suggest a lymphoid cell expressing T- and/or B-cell-associated markers and certain activation antigens while lacking immunological features of monocytes-macrophages or other lineages. Molecular genetic studies have demonstrated heterogenous findings with respect to rearrangements of T-cell receptor and immunoglobulin genes. Only a small percentage of the cases has rearrangements; this might be due to the threshold of sensitivity of the method combined with the scarcity of the malignant cells. Epstein-Barr virus (EBV) genomes are clonally integrated in the H-RS cells of about half the cases. The significance of these findings—whether EBV is a causative agent or an epiphenomenon—remains to be elucidated. H-RS cells express mRNA and proteins of various cytokines and cytokine receptors implying a predominant role for cytokines in the pathophysiology of HD. The mononuclear and polynuclear H-RS cells are capable of DNA synthesis and nuclear division; the lack of cellular division leads to multinuclearity through the process of endomitosis. Mutations and expression of only a limited number of oncogenes have been tested thus far. Whether the bcl-2 oncogene is involved in HD remains a matter of debate. Aneuploidy and non-random chromosomal abnormalities are the results of cytogenetic analyses of H-RS cells. However, no chromosomal marker specific for HD has yet been found. Thus, while studies of EBV involvement, growth factor production, oncogene expression and chromosomal abnormalities contributed a fair amount of new data on the nature of H-RS cells, only immunophenotyping and genotyping provided some indication of the cellular derivation: an activated lymphoid cell that possibly expresses oncogenes, that probably is infected with EBV, that most likely produces cytokines, that certainly has multiple karyotypic abnormalities.     

Imbalances of chemokines,chemokine receptors and cytokines in Hodgkin lymphoma: classical Hodgkin lymphoma vs. Hodgkin-like ATLL

Classical Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. We previously reported Hodgkin-like adult T-cell leukemia/lymphoma (HL-like ATLL) (new WHO classification). Various CXC and CC chemokines are expressed on H&RS cells and the relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity of Th1 and Th2 T cells. To clarify the role of T-cell immunity in classical HL and Hodgkin-like ATLL, we performed gene expression profiling (chemokine, chemokine R and cytokine DNA chips) in 12 cases [classical HL, 8 cases [mixed cellularity (MC) type, 4; nodular sclerosis (NS) type, 4]; Hodgkin-like ATLL, 4 cases] and immunohistochemical staining in 29 cases (MC, 10; NS, 10; Hodgkin-like ATLL, 9). EBV-infected H&RS cells were detected in 9 of 10 cases of HL MC, 5 of 9 of HL-like ATLL and 2 of 10 HL NS. T-cell-directed chemokine thymus- and activation-regulated chemokine (TARC)- and/or macrophage-derived chemokine (MDC)-positive H&RS cells were detected in all 20 cases of HL MC and HL NS but only in 5 of 9 cases of HL-like ATLL. Interferon-gamma-inducible protein-10 (IP10)- and monokine induced by interferon-gamma (MIG)-positive H&RS cells were detected in all 10 HL MC but only in 5 of 10 cases of HL NS and 2 of 9 cases of HL-like ATLL. However, 2 of 5 cases of HL-like ATLL with EBV infection and 2 of 2 HL NS with EBV had IP10/MIG-positive H&RS cells. The chemokine expressions in H&RS cells seemed to be associated with EBV infection rather than histologic subtypes. In the DNA chip expression analysis, classical HL and HL-like ATLL had a mixed Th1/Th2-type profile, and HL MC (EBV-positive) and HL NS (EBV-negative) were differentially clustered. However, 2 cases of HL-like ATLL clustered with HL MS and the other 2 cases of HL-like ATLL clustered with HL NS. The former HL-like ATLL had EBV infection in H&RS cells, whereas the latter did not have EBV infection. This finding also suggests that EBV might influence local expression of chemokines rather than HL subtypes. Our results indicate that local immunologic disorder or imbalance appears to influence the formation of H&RS cells and that in HL-like ATLL, HTLV-1 infection might not be necessary for H&RS cell formation.     

Primary adenocarcinoma of the esophagus

Of 163 patients with carcinomas of the esophagus seen between 1975 and 1982, 11 (6.7%) had a primary adenocarcinoma. Although the high ratio of men to women (10:1) was similar to that seen in patients with squamous cell carcinoma of the esophagus, the mean age of those with adenocarcinoma was younger (57 years). In contrast to squamous cell carcinomas, which predominantly involve blacks, esophageal adenocarcinomas in these patients involved only Caucasians. The great majority of lesions were found in the lower third of the esophagus. Only 3 (27%) of the patients with adenocarcinomas gave a history of a large daily alcohol consumption and only 2 (18%) had a Barrett's esophagus. Although various combinations of surgery, chemotherapy, and radiotherapy could control the primary tumor rather well, the final results were poor. All patients have now expired; median survival time was 16 months.     

Genetic polymorphisms in DNA repair genes as modulators of Hodgkin disease risk

BACKGROUND:

Although the pathogenesis of Hodgkin disease (HD) remains unknown, the results of epidemiologic studies suggest that heritable factors are important in terms of susceptibility. Polymorphisms in DNA repair genes may contribute to individual susceptibility for development of different cancers. However, to the authors' knowledge, few studies to date have investigated the role of such polymorphisms as risk factors for development of HD.

METHODS:

The authors evaluated the relation between polymorphisms in 3 nucleotide excision repair pathway genes (XPD [Lys751Gln], XPC [Lys939Gln], and XPG [Asp1104His]), the base excision repair XRCC1 (Arg399Gln), and double‐strand break repair XRCC3 (Thr241Met) in a population of 200 HD cases and 220 matched controls. Variants were investigated independently and in combination; odd ratios (OR) were calculated.

RESULTS:

A positive association was found for XRCC1 gene polymorphism Arg399Gln (OR, 1.77; 95% confidence interval [95% CI], 1.16‐2.71) and risk of HD. The combined analysis demonstrated that XRCC1/XRCC3 and XRCC1/XPC polymorphisms were associated with a significant increase in HD risk. XRCC1 Arg/Arg and XRCC3 Thr/Met genotypes combined were associated with an OR of 2.38 (95% CI, 1.24‐4.55). The XRCC1 Arg/Gln and XRCC3 Thr/Thr, Thr/Met, and Met/Met genotypes had ORs of 1.88 (95% CI, 1.02‐4.10), 1.97 (95% CI, 1.05‐3.73), and 4.13 (95% CI, 1.50‐11.33), respectively. XRCC1 Gln/Gln and XRCC3 Thr/Thr variant led to a significant increase in risk, with ORs of 3.00 (95% CI, 1.15‐7.80). Similarly, XRCC1 Arg/Gln together with XPC Lys/Lys was found to significantly increase the risk of HD (OR, 2.14; 95% CI, 1.09‐4.23).

CONCLUSIONS:

These data suggest that genetic polymorphisms in DNA repair genes may modify the risk of HD, especially when interactions between the pathways are considered. Cancer 2009. © 2009 American Cancer Society.     

贲门失弛症并发食管癌与贲门癌

目的提高贲门失弛症并发食管、贲门癌的诊断和治疗水平.方法回顾12例贲门失弛症伴发食管、贲门癌的诊断治疗和病理.结果 12例贲门失弛症伴发食管、贲门癌病例中,手术治疗4例,其中2例生存超过3年.1例于手术后半年死亡,1例术后不足半年,放化疗6例,均于半年至一年半内死亡.结论 1.食管、贲门癌易被贲门失弛症的症状所掩盖.2. Heller手术并不能降低食管癌的发生率,应每年随访1次. 3.贲门失弛症伴发食管癌发生比率较高,也是食管癌的高发人群.4 .术后病人如有症状早就诊可以早期发现.5 .同时发生癌和异时发生癌的机会相近.Heller术前应常规内镜检查排除食管贲门癌以防漏诊.     

环咽肌切断术在鼻咽癌及颅脑肿瘤治疗后环咽肌失弛缓症中的应用

背景与目的：目前治疗环咽肌失弛缓症的方法较多,但有些治疗方法患者的依从性较差,有些治疗方法需长期腹部带管,同时容易出现造瘘口周围感染。本文探讨环咽肌切断术在鼻咽癌及颅脑肿瘤治疗后环咽肌失弛缓症中应用的有效性及可行性。材料与方法：2005年6月至2010年1月诊断为环咽肌失弛缓症患者8例,其中鼻咽癌放疗后6例,颅脑肿瘤术后2例。结果：8例患者均接受环咽肌切断术,术后患者可进食固体或软食,进食时间缩短,体重增加。结论：环咽肌切断术是治疗鼻咽癌及颅脑肿瘤治疗后环咽肌失弛缓症的有效手段,可明显改善患者吞咽困难症状,提高生存质量。     

Nurses provide valuable proxy assessment of the health‐related quality of life of children with Hodgkin disease

BACKGROUND:

We prospectively compared the proxy reporting of health‐related quality of life (HRQL) by parents and nurses of children with Hodgkin disease to see how well they correlated with the children's report.

METHODS:

Children with all stages of Hodgkin disease, their parents, and the clinic nurse were all asked to complete 4 different HRQL measures at 4 time points: 2 weeks after the first course of chemotherapy, on the third day of the second course of chemotherapy, during the third week of radiation, and 1 year after diagnosis.

RESULTS:

Fifty‐one patients from 12 centers across Canada were enrolled in the study between May 1, 2002 and March 31, 2005. Two patients were excluded. The children's Pediatric Quality of Life Inventory (PedsQL) generic scores increased from 64 at base line to 81 at the end of the study. There was substantial agreement (intraclass correlation coefficient >0.6) among the participants' scores at most time points except when the child was actively receiving inpatient chemotherapy. At that time, there was only fair to moderate agreement between the child and parent, with the parents on average rating the PedsQL generic score 5 points lower than the child. The nurses still had substantial agreement at that time point with the PedsQL generic and cancer module as well as the EuroQol EQ‐5D visual analogue scale visual analogue scale.

CONCLUSIONS:

Over the course of treatment for Hodgkin disease, there was substantial agreement among the parent's, nurse's, and children's reported HRQL scores. Nurses contribute valuable additional information as proxy respondents. Cancer 2010. © 2010 American Cancer Society.