Der chirurgische Part im Rahmen multimodaler Therapiekonzepte in der Onkologie-Schilddrüse

29. Tagung der ?sterreichischen Gesellschaft für Chirurgie und Ihrer Assoziierten Fachgesellschaften Innsbruck, 2. bis 4. Juni 1988 Herausgeber: E. Bodner und G. Szinicz Abstracts

Der chirurgische Part im Rahmen multimodaler Therapiekonzepte in der Onkologie-Schilddrüse     

The fludarabine,cytarabine, and granulocyte colony‐stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline‐based therapy for the treatment of acute myeloid leukemia for patients with pre‐existing cardiac disease

We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and granulocyte colony‐stimulating factor) as first‐line treatment in 56 newly diagnosed acute myeloid leukemia patients considered ineligible for anthracycline‐based treatment due to advanced age, significant comorbidities, or pre‐existing cardiac disease. The median age was 69 (21–80); 46% received FLAG for pre‐existing cardiac disease and others due to age (32%), non‐cardiac comorbidities (20%), or previous anthracycline exposure (2%). The induction mortality was 16% and, among evaluable patients, 48% achieved a complete remission after the first induction course with an additional patient achieving a remission after a second course for a total complete remission rate of 50%. Four patients proceeded to an allogeneic stem cell transplant including two with pre‐existing cardiac disease. Among non‐transplanted patients, the relapse rate (RR) was 47%. When censored at time of stem cell transplant, the median relapse‐free survival was 14.7 months. The median overall survival was 9.3 months with 1‐ and 2‐yr survivals of 44% and 22%, respectively. There was no difference in clinical outcomes between patients treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a useful alternative to anthracycline‐based induction for Acute myeloid leukemia in those with significant comorbidities including pre‐existing cardiac disease.     

Spouse Beliefs About Partner Chronic Pain

Although research has shown that patients' beliefs about their pain are related to pain adjustment and treatment outcomes, little is known about the beliefs of their significant others. The purpose of this study was to develop a measure of pain beliefs in significant others and to examine the correlates of these beliefs. Participants were 104 married couples in which 1 partner reported chronic pain. Spouses completed an amended version of the Survey of Pain Beliefs (SOPA). The scale development procedure described in Jensen et al was used to select appropriate items for the significant other version of the SOPA. This procedure yielded 7 subscales that closely resembled the original SOPA. Spousal pain beliefs about disability, emotion, control, and medication were significantly correlated with partners' pain severity and other indicators of pain adjustment. Emotion, disability, and other beliefs were related to spouse responses to pain, and spouses' depressive symptoms and marital dissatisfaction. Spouses' personal experiences with pain were not related to their beliefs about their partners' pain. Additional research on the pain-related beliefs of significant others may extend cognitive-behavioral theory concerning the social context of pain and provide an additional avenue through which clinicians can address cognition in patients and families.PerspectiveThis study describes a new measure that can be used to assess significant others' beliefs about their partners' pain problems. Little is known about the beliefs of family members so this measure is expected to provide a way for clinicians and researchers to assess and track changes in those beliefs.     

Simultaneously presenting head and neck and lung cancer: a diagnostic and treatment dilemma.

OBJECTIVES/HYPOTHESIS: Synchronous tumors are defined as malignancies presenting within 6 months of the index tumors. A significant subset of patients present at initial evaluation with malignant tumors of both the head and neck (head and neck squamous cell carcinoma) and the lung, which are termed simultaneous primaries. The management and treatment outcomes in this cohort of patients have not been clearly defined and are the subject of the present review. STUDY DESIGN: Retrospective chart review of previously untreated patients. METHODS: From January 1974 to December 1997, a total of 2964 patients were treated for mucosal squamous cell carcinoma of the head and neck. Forty-two patients fulfilled the criteria for synchronous head and neck and lung malignancy. Of these, 27 patients had simultaneous tumors of the head and neck and the lung. This cohort of patients (n = 27) was stratified into three treatment groups. Patients in group A (n = 10) had resectable head and neck and lung primaries treated with curative intent. Group B (n = 8) was composed of patients who could have been treated with curative intent but declined and were given only palliative therapy. Patients in group C (n = 9) were candidates for only palliative treatment. RESULTS: The estimated 5-year disease-specific survival in group A was 47%, whereas patients in group B had a 5-year disease-specific survival of only 13% (P =.05). There were no survivors beyond 1 year in group C. The presence of mediastinal adenopathy in patients in group A portended poor clinical outcome. There was an estimated 5-year disease-specific survival of 51% in patients with no preoperative evidence of mediastinal adenopathy (n = 7), whereas 67% of patients with radiological evidence of mediastinal adenopathy died (two of three patients). CONCLUSION: The presence of simultaneous head and neck squamous cell carcinoma and pulmonary malignancies should not be a deterrent to aggressive surgical therapy because a potentially satisfactory outcome can be expected in these patients.     

Molecular prognosticators and genomic instability in papillary thyroid cancer

OBJECTIVES/HYPOTHESIS: Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer. STUDY DESIGN: Prospective analysis. METHODS: GSTM1 and GSTT1 genotypes of 35 matched normal and papillary thyroid cancer specimens were determined by polymerase chain reaction (PCR) using primers specific for the coding sequences of each gene. Genomic instability was measured by intersimple sequence repeat PCR for each tumor/normal pair and compared with the GAMES prognostic scoring system and clinicopathologic parameters including age, extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking history. RESULTS: GSTM1 and GSTT1 null genotypes were found in the normal tissues of 46% and 45%, respectively. No gene losses were detected in the tumor specimens. A significant association between the GSTM1 null genotype and increased risk of recurrence and death was observed. Elevated GII correlated with smoking and tumor stage but not with GST genotype. CONCLUSION: The association of GSTM1 null genotype with intermediate and high risk GAMES categories suggests that GSTM1 provides some protection against disease progression. However, this protection does not confer resistance to disease onset. GST genotyping may be a useful adjunct prognosticator with GAMES.     

Sentinel lymph node biopsy: a rational approach for staging T2N0 oral cancer

OBJECTIVES/HYPOTHESIS: For oral cancer patients, the presence of neck nodal metastases is the most important disease prognosticator. However, a significant proportion of clinically N0 patients harbor occult microscopic nodal metastasis. Our objective was to determine the feasibility and accuracy of sentinel node biopsy (SNB) in the staging of T2N0 oral carcinoma patients. STUDY DESIGN: Prospective analysis. METHODS: Twenty patients with previously untreated N0 oral cavity squamous cell carcinoma were studied. Each patient had an SNB performed using preoperative technetium sulfur colloid lymphoscintigraphy, intraoperative gamma probe guidance, and intraoperative peritumoral injection of 1% isosulfan blue. All patients underwent neck dissection.The sentinel lymph nodes (SLNs) were sectioned in 2- to 3-mm intervals, formalin fixed, and sectioned at three levels. The non-SLNs were sectioned in a routine manner for histologic examination. RESULTS: SLNs were identified in all patients (100%) and accurately predicted the pathologic nodal status in 18 of 20 patients (90%). Tumor was found exclusively in the SLNs in six patients (30%). Two patients had positive SLNs at multiple neck levels. Two patients had a negative SLN and a positive non-SLN (false-negative findings). Occult nodal metastases were present in 60% of the cohort. CONCLUSIONS: SNB is a technically feasible and accurate procedure for staging the neck in oral carcinoma patients. However, SNB accuracy is lower for floor of the mouth lesions. The rate of occult nodal metastases identified in this cohort is higher than previously reported in the literature. These results suggest that SNB warrants further multi-institutional studies.     

The path of least resistance: is there a better route?

In May 2000, the radiology department at Stanford University Medical Center embarked on a five-year journey toward complete digitization. While the end goal was known, there was much less certainty about the steps involved along the way. Stanford worked with a team from GE Medical Systems to implement Six Sigma process improvement methodologies and related change management techniques. The methodical and evidence-based framework of Six Sigma significantly organized the process of "going digital" by breaking it into manageable projects with clear objectives. Stanford identified five key areas where improvement could be made: MR outpatient throughput, CT inpatient throughput, CT outpatient throughput, report turnaround time, and Lucile Packard Children's Hospital CR/Ortho throughput and digitization. The CT project is presented in this article. Although labor intensive, collecting radiology data manually is often the best way to obtain the level of detail required, unless there is a robust RIS in place with solid data integrity. To gather the necessary information without unduly impacting staff and workflow at Stanford, the consultants working onsite handled the actual observation and recording of data. Some of the changes introduced through Six Sigma may appear, at least on the surface, to be common sense. It is only by presenting clear evidence in terms of data, however, that the improvements can actually be implemented and accepted. By converting all appointments to 30 minutes and expanding hours of operation, Stanford was able to boost diagnostic imaging productivity, volume and revenue. With the ability to scan over lunch breaks and rest periods, potential appointment capacity increased by 140 CT scans per month. Overall, the CT project increased potential for outpatient appointment capacity by nearly 75% and projected over $1.5 million in additional annual gross revenue. The complex process of moving toward a digital radiology department at Stanford demonstrates that healthcare cannot be healed by technology alone. The ability to optimize patient services revolves around a combination of leading edge technology, dedicated and well-trained staff, and careful examination of processes and productivity.     

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction

BACKGROUND: In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution. DESIGN: Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter-simple sequence repeat polymerase chain reaction. RESULTS: The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter-simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations. CONCLUSIONS: At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.     

The role of supraomohyoid neck dissection in patients with positive nodes

BACKGROUND: Supraomohyoid neck dissection (SOHND) is currently used as a staging procedure for patients with clinically negative nodes in the neck who are at increased risk (>20%) for metastatic disease. OBJECTIVE: To assess the potential role of SOHND in patients with clinically positive nodes at levels I, II, or III. We evaluated, in particular, whether selective neck dissection in patients with clinically positive nodes results in decreased regional control and/or diminished survival. PATIENTS AND METHODS: We retrospectively reviewed the charts of all patients who underwent SOHND from January 1, 1971, to December 31, 1997. The oral cavity and oropharynx represented the primary sites in the majority of the patients. Two-year follow-up information was available on all patients. RESULTS: During the study period, 69 patients underwent 84 SOHNDs. Of the 69 patients, there were 30 patients with clinically negative nodes and 39 patients with clinically positive nodes in the neck. The overall regional control rates were 88% vs 71% for pathologically negative vs positive nodes, respectively, with or without adjuvant radiation therapy. Adjuvant radiation therapy significantly improved regional control in patients with pathologically positive nodes but not in patients with NO disease (P = .005). Similar results were noted in patients with both clinically and pathologically positive nodes. CONCLUSIONS: Supraomohyoid neck dissection in patients with pathologically positive nodes in the neck is inadequate therapy for regional control without postoperative radiation therapy. However, in patients with pathologically positive nodes in the neck, SOHND with postoperative radiation therapy can achieve regional control comparable to that of comprehensive neck dissection and postoperative radiation therapy.