肺癌患者的多原发恶性肿瘤

目的：总结肺癌患者多原发恶性肿瘤的诊断和治疗经验。方法：分析肺癌患者多原发恶性肿瘤４５例的临床病理资料,占同期手术病理证实１８３６例肺癌的２．５％。男３８例,女７例。多原发肺癌１６例,占０．９％,其中１５例为双原发癌,１例为三原发癌;肺癌与其他脏器恶性肿瘤２９例,占１．６％,其中２７例为双原发恶性肿瘤,２ 三原发癌。结果：多原发肺癌患者术后３和５年生存率为６０．０％（６／１０）和４４．４％（４／９     

Case of simultaneous multiple primary lung cancer

The incidence of multiple primary bronchogenic carcinomas has increased in Japan as the incidence of bronchogenic malignancy has increased. The patient was a 71-year-old man with simultaneous multiple bronchogenic carcinomas. He had large cell carcinoma in the left upper lobe and adenocarcinoma in the left lower lobe. We reviewed 66 reported Japanese cases with multiple lung cancers with special reference to sex distribution, age, simultaneous or metachronous, location, histological types, treatment and prognosis.     

Outcome of patients receiving photodynamic therapy for early esophageal cancer

PURPOSE: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.     

Sequential loss of heterozygosity in the progression of squamous cell carcinoma of the lung.

Radiographically occult bronchogenic squamous cell carcinomas are early lung cancers that localize mainly in the bronchial wall, and are thought to be a good model for investigating genetic alterations through lung cancer progression. In order to elucidate sequential genetic changes in lung cancers, we analysed the incidence of allelic losses on chromosome regions 2q33, 3p21, 5q21, 7q31, 9p21 and 17p13 for 40 cases of radiographically occult bronchogenic squamous-cell carcinomas and 40 cases of advanced lung cancers microdissected. In this study we used eight microsatellite dinucleotide polymorphic markers. Frequent loss of heterozygosity (LOH) was observed on 3p21 (53%), 5q21 (44%) and 17p13 (61%) in roentgenographically occult bronchogenic squamous cell carcinomas. 2q, 7q and 9p were lost less frequently in both roentgenographically occult bronchogenic squamous cell carcinomas and advanced lung cancers. These results suggest that several tumour-suppressor genes are associated with lung cancer progression and that genetic changes on 3p21, 5q21 and 17p13 are early events.     

食管多原发癌8例临床分析

目的通过分析食管多原发癌的临床病理特征及预后,探讨食管多原发癌的诊断和治疗措施。方法回顾性收集自2000年10月至2008年1月经右胸行En-bloc切除的食管多原发癌患者的临床病理资料和随访结果,分析食管多原发癌的临床病理特点及预后,并结合国内外近年来相关文献,对其诊断和治疗措施进行讨论。结果食管多发癌的发生率为9.6%。8例患者皆为男性,7例吸烟大于20包/d×年,4例嗜酒。病理皆为鳞癌。主癌灶多累及食管全层,次癌灶多为原位癌,部分病例伴有上皮不典型增生。全部患者接受食管癌En-bloc切除及胃食管左颈吻合术。1,3年生存率分别为62.5%和12.5%,中位生存期13个月。结论食管多原发癌的发生是区域癌化的结果;采用Lugol碘液染色下胃镜活检可提高食管多原发癌诊断率;行全食管切除可减少食管癌术后复发率;食管多原发癌发现时多偏晚期,预后较差。     

Surgical treatment of the second primary lung cancer

1168 patients with primary carcinoma of lung had been treated by surgery in our hospital from 1976 to 1985. Among these patients we found 7 patients with second primary lung cancer. The incidence is 0.6% in this series. The criteria of the second primary lung cancer are: different histological type; synchronous lesion located in the contralateral lung or in different lobes or segments of the ipsilateral lung which must all be stage I; or prolonged interval between the initial and second resection (metachronous lesions), but the initial lesion must be proved as stage I. Lobectomy was the most common procedure for the initial and second resections. The result of the treatment was satisfactory with one patients surviving 6 years and 6 months. There was no operative mortality or complications. We consider that careful diagnosis is important and continued follow-up is necessary for all bronchogenic carcinomas.     

Clinical and pathological studies of multiple primary carcinoma of the colon and rectum

During a 5-year period from 1976-1981, we clinicopathologically studied 21 patients with 45 lesions of multiple primary colorectal carcinomas and compared our findings with those made in 288 single carcinomas of the large intestine. The frequency of multiple primary colorectal carcinoma was 6.8%. The pathological findings suggested an interrelationship between colorectal adenoma and carcinoma. Patients with multiple carcinomas of the large bowel had coexisting adenomas more than patients with single carcinoma. We suggest that it is necessary to do a thorough preoperative examination of cancer of the large intestine to detect double cancers or other adenomatous polypoid lesions with synchronous association.     

Early hilar lung cancer--risk for multiple lung cancers and clinical outcome.

In early hilar lung cancer patients, multiple lung cancers frequently develop. The clinical outcome of such patients were studied. A total of 91 patients, 88 men and three women, who were endoscopically diagnosed with early hilar lung cancer were studied retrospectively. Surgery was performed in 46 patients, while organ-sparing treatment, including photodynamic therapy (PDT), Nd-YAG (neodymium-yttrium, argon, garnet) laser vaporization, and radiotherapy, were done for 45 patients. During follow-up, newly developed lung cancers and/or malignancies in other organs were recorded. The average smoking index (cigarettes per day x years) was 1040. Synchronous and/or metachronous multiple lung cancers developed in 26/91 patients (28.6%). Malignancies in other organs were found in 12/91 (13.2%). The smoking index of patients with multiple lung cancers was significantly higher than for other patients. The overall 5 year survival rate was 70.7% in all patients, 76.0% in the surgery group, and 64.4% in the nonsurgery group. The lung cancer-specific 5 year survival rate was 89.8% in all patients, 89.3% in the surgery group, and 90.5% in the nonsurgery group. Early hilar lung cancer frequently accompanies other lung cancers or malignancies in other organs. A favorable prognosis can be obtained with organ-sparing treatment.     

Clinical outcomes of photodynamic therapy for head-and-neck cancer

Head-and-neck cancers not only carry poor prognoses, but also reduced quality of life for the patients. Disease control is often achieved at the expense of substantial functional loss and disfigurement. Photodynamic therapy (PDT) is particularly well suited to the treatment of head-and-neck-tumors because it has little effect on underlying functional structures and has an excellent cosmetic outcome. Studies in the past decades have shown that PDT is of similar efficacy as traditional measures in the treatment of early-stage head-and-neck cancers with an overall response rate of 85%-100% with up to 75% of the complete responses sustained at 2 years after PDT. For advanced head-and-neck cancers, studies were also conducted to evaluate the palliative effects of PDT. Overall, 58%-70% palliative benefit can be observed in these patients. Using interstitial PDT, median survival of the patients with recurrent unresectable head-and-neck cancers can be improved to 14 months (cf. 226 days by using surface illumination PDT). PDT is thus a therapeutic option that may prove a useful addition to the armamentarium of the integrated head and neck oncology team.     

Phase II clinical study of photodynamic therapy using mono-L-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. A second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) has shown anti-tumor efficacy and rapid clearance from skin. Therefore, we conducted a phase II clinical study to investigate the anti-tumor effects and safety of NPe6 in patients with early superficial squamous cell carcinoma of the lung. Enrollment criteria consisted of endoscopically evaluated early stage lung cancer with normal chest X-ray and CT images, no lymph node or distant metastasis. Tumors were located no more peripherally than subsegmental bronchi, the peripheral margin had to visible, and the tumor size had to not more than 2 cm in diameter. The histologic type of the tumor had to squamous cell carcinoma. Laser irradiation (100 J/cm2) using a diode laser was performed at 4 h after administration of NPe6 (40 mg/m2). Among 41 patients with 46 lesions, 40 with 45 lesions were eligible for safety evaluation, and 35 patients with 39 lesions were judged as eligible for efficacy evaluation. No serious adverse drug reactions were observed. Disappearance of skin photosensitivity was recognized within 2 weeks in 28 of 33 patients (84.8%) and in all the other seven patients first tested at 15-18 days. Complete response (CR) was seen in 84.6% of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety, especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT for central type early superficial squamous cell carcinoma of the lung.     

Morphology of bronchogenic carcinoma in workers formerly exposed to crocidolite at Wittenoom Gorge in Western Australia

Cytology and histology material from 46 bronchogenic carcinomas occurring in ex-workers from the Wittenoom crocidolite mine and mill in Western Australia and a matched random sample of 234 other bronchogenic carcinomas occurring in Western Australia over the same period were reviewed by a single histopathologist without knowledge of asbestos exposure status. Squamous-cell carcinomas formed 45.7% of the cancers in the asbestos-exposed group but only 32.5% of the cancers in the comparison group. This difference could not be explained by differences in smoking history between the two groups of lung cancer patients or in the type of histopathological material available for review. The excess of squamous-cell cancers was observed in subjects both with and without parenchymal asbestosis.     

Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung

Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large "test" set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.     

Clinical study of multiple primary cancers including lung cancer

Out of a total of 506 lung cancers treated between 1977 to 1988, a total of 27 (5.3%) multiple primary cancers were uncovered. The patients consisted of 20 males and 7 females and their average age was 67 (48-81) years. The frequency seen in the histological type of patient with multiple primary cancers was the same as that seen in their background lung cancers. Twenty-one (78%) patients were smokers. Thirteen patients (45%) had a family history of cancer. Two cases had 3 family members who had a cancer history. The tumor DNA contents of 2 cases with multiple primary cancers were analyzed. In both cases, the DNA indices were found to differ between the first and the second cancer. Thus, it may be possible to identify multiple primary cancers by determining the tumoral DNA content.     

A clinicopathological study of multiple thyroid carcinomas

Thyroid cancers associated with multiple cancerous lesions that were detected by clinical and/or histological examination, namely, multiple thyroid carcinomas have been studied clinicopathologically. Of 443 cases of primary thyroid cancers, 111 (25%) had multiple cancerous lesions. Histologically, most multiple cancers consisted of papillary carcinomas. In 66% of the cases, the size of the second cancer was 1.0 cm or less. Fifty-three percent of multiple cancers were located in both the right and left thyroid lobes. Therefore, it is important to examine the contralateral lobe at operation to be certain that there are no other nodular lesions. Since lymph node metastasis was positive in 83% of the cases, it is necessary to perform bilateral neck dissection in multiple cancer cases of not only the bilateral but also of the unilateral type.     

Clinical Outcomes and Safety Profile in the Treatment of Synchronous Nonmetastatic Lung Tumors With Stereotactic Body Radiation Therapy

PurposeStereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients.Methods and MaterialsWe queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume.ResultsWe analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis).ConclusionsSynchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors.     

Role of lung transplantation in the treatment of bronchogenic carcinomas for patients with end-stage pulmonary disease.

PURPOSE: To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease. METHODS: An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers. RESULTS: Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma. CONCLUSION: This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.     

Photodynamic therapy for peripheral lung cancer

Photodynamic therapy (PDT) has now achieved the status of a standard treatment modality for centrally located early-stage lung cancer. In the last decade, CT screening for lung cancer has attracted much attention for its ability to detect early peripheral lung cancer. Extremely recently, treatment using PDT has been introduced for the first time in patients with peripheral lung cancer, who did not meet the previous criteria for surgery. The procedure was carried out with local anesthesia with xylocain infiltrated into the chest wall, 48 h after Photofrin administration. Needles (19 gauge) containing an internal catheter were inserted percutaneously under CT guidance. The needles were then extracted and a diffuser fiber with a 2 cm long tip for light delivery was positioned in the tumor through the catheter. Of the nine patients enrolled in this trial, seven achieved partial remission (PR). No serious complications, except for two cases of pneumothorax, were noted. As an increasing number of patients consider quality of life after therapy, the indications for PDT are expected to expand. We conclude that PDT is a promising new technique for curative treatment of localized, peripheral lung cancer less than 1cm in size in patients who are unfit for surgery or radiotherapy.     

Accelerated hyperfractionation in patients with non-small cell bronchogenic cancers as a cost-effective and user- and patient-friendly schedule

We developed an accelerated hyperfractionation schedule with acceptable effect and toxicity in non-small cell bronchogenic carcinomas. An evolutionary institutional pilot was initiated in March 1995 as a modification of Radiation Therapy Oncology Group (RTOG) 9205, thrice-daily fractionation schedule. Twenty-nine patients with bronchogenic and 7 with head and neck cancers had treatment initiated and completed. A dose of 1.2 Gy was delivered to a mediastinal plus tumor field concomitantly with synchronous boost of 0.6Gy to a limited volume of gross tumor (twice daily for 27 treatments days in 4 weeks) with a total dose being 75.60 Gy to the primary gross tumor and 50.4 Gy to the elective volume. The bronchogenic cancers were stages IB (medically unresectable, n = 3), IIB (n = 4), IIIA (n = 4), or IIIB (n = 18). Eleven patients had squamous cell cancers, 13 adenocarcinomas, 1 large cell, and 2 carcinomas not specified. With 12 months median follow-up, tolerance has been excellent without any patient complaining of at least Oncology Nursing Society (ONS) grade 3 esophagitis; treatment interruptions occurred in only one patient after 8 days. Weight loss occurred in 12 patients, averaging 4.8% for these patients and 2% overall. Seven patients had a complete response and 20 a partial response. Median survival was 12 months, 1-year survival 58%, 2-year 21%, and 3-year 18%. Seven patients with bronchogenic cancer are still alive. Seven head and neck cancer patients were treated, in which five had base of tongue tumors stage T2 to 4, NO to N1. Pharyngitis and mucositis were problematic in at least four patients. The outcomes are comparable with other RTOG experience. Hyper-fractionated synchronous concomitant boost of total tumor dose to 75.6 Gy in 4 weeks for bronchogenic patients was well tolerated and acceptable to physicians and patients.