A case of genital Paget's disease with severe dermal invasion and early dissemination]

A 65-year-old man was referred to our hospital with a complaint of a scrotal mass which he first noticed 8 months ago. The mass was resected saving genital organs. Pathological diagnosis was extramammary Paget's disease with severe dermal invasion and many nuclear mitoses. The tumor was 15 mm in diameter, and 18 mm in thickness. The bilateral inguinal lymph nodes were dissected and multiple metastases were revealed in the right specimen. Since paraaortic lymph node metastases were detected later 5 cycles of chemotherapy consisting of cyclophosphamide, adriamycin and cisplatin (CAP) followed by radiation therapy were performed. However, only a partial response could be obtained, and multiple brain metastases were revealed on computed tomographic scan. He died 22 months after discovery of this disease. Since extramammary Paget's disease tends to grow slowly and horizontally, cases with such severe dermal invasion and early dissemination as in our case are unusual.     

Thermochemotherapy in inoperable head and neck cancer

A combined hyperthermia and chemotherapy approach was used to treat five patients with locally advanced or recurrent squamous cell carcinoma of the head and neck whose tumors had failed to respond to chemotherapy. In two patients, tumor had recurred after initial combined modality therapy (surgery/radiation) and had failed to respond to one course of cisplatin/5-fluorouracil (cisplatin/5-FU) chemotherapy. The three remaining patients were enrolled onto a phase II evaluation of induction chemotherapy with cisplatin/fluorouracil for advanced head and neck carcinomas and had failed to achieve a partial remission after one treatment cycle. Palpable cervical tumors were heated to 40 degrees to 42 degrees C for 30 to 40 minutes, during which time cisplatin (100 mg/m2) was infused intravenously. A 5-day infusion of 5-fluorouracil (1000 mg/m2/d) followed. Despite less than a partial response to previous cisplatin/fluorouracil chemotherapy alone, two patients had complete clinical resolution of the heated tumor volume with two cycles of the combined thermochemotherapy approach. One patient achieved a partial remission with this approach. The remaining two patients died shortly after the initial thermochemotherapy treatment, as a result of progressive tumor growth. The two complete responders were subsequently treated with radiation (1 patient) and radical neck dissection (1 patient) and remained without evidence of disease 2 and 26 months after the completion of therapy, respectively. The toxicity of this combined modality approach was acceptable and appeared to be no greater than had been experienced during earlier treatment with chemotherapy alone. Further studies using a combination of these treatment modalities for locally advanced head and neck carcinomas are warranted.     

Basaloid-Squamous Carcinoma of the Esophagus Treated by Preoperative Chemotherapy: Report of Two Cases

Basaloid squamous carcinoma (BSC) of the esophagus has been associated with a poor outcome after surgery. We herein report two patients with esophageal BSC treated by preoperative chemotherapy. Patient 1 was a 55-year-old man who presented with a tumor of the middle esophagus diagnosed as BSC. He was treated by chemotherapy using a combination of 5-fluorouracil (5-FU: 750 mg/m², 1st–5th day, 24-h continuous infusion) and cisplatin (CDDP: 75 mg/m², 1st day, drip infusion per 2 h) before surgery, because of lymph node metastases of the mediastinum and around the left gastric artery. Even though the metastatic nodes were reduced and an esophagectomy was performed, the patient died of recurrence 12 months after chemotherapy. Patient 2 was a 57-year-old man who demonstrated BSC of the esophagus with direct invasion to the discending aorta, who was treated by preoperative chemotherapy using the same regimen as that of patient 1. The esophageal tumor was reduced, and a curative esophagectomy was performed. The patient is now alive without recurrence 38 months after chemotherapy. In conclusion, preoperative chemotherapy using a combination of 5-FU and CDDP may thus be an effective treatment for patients with advanced BSC of the esophagus. Received: September 19, 2001 / Accepted: May 7, 2002 RID="*" ID="*" Reprint requests to: N. Koide     

The prognostic value of lymph node metastases and tumour regression grade in rectal cancer patients treated with long-course preoperative chemoradiotherapy

Objective  The purpose of the present study was to investigate the impact of tumour regression and the post-treatment lymph node status on the prognosis of rectal cancer treated by preoperative neoadjuvant chemoradiotherapy.
Method  One hundred and thirty-five patients with locally advanced T3 and T4 rectal tumours received preoperative long-course chemoradiation, to a dose of 60 Gy external radiation and oral 5-fluorouracil 300 mg/m² daily and Leukovorin 22.5 mg/day 5 days a week. Surgery was performed 8 weeks after the end of treatment. The tumour response was evaluated according to the tumour regression grade system and lymph node status in the surgical specimen was assessed. The prognostic value of clinico-pathological parameters was analysed using univariate analysis and Kaplan–Meier methods for comparison of groups.
Results  All patients responded to treatment and 47% had a major response, including 25 (19%) complete responders. The median follow-up was 26 months (range 12–94 months). The cancer specific survival was 82% and there was a significant lower survival rate in the group of patients with post-treatment lymph node metastases compared to lymph-node negative patients [63% and 87% respectively ( P  = 0.007)]. Furthermore patients with a major tumour response and no lymph node metastases in the surgical specimen after treatment had a survival rate of 100% compared with 60% in the group of patients with major response but lymph node metastases after surgery ( P  < 0.01).
Conclusion  The combined assessment of lymph-node status and tumour response has strong prognostic value in locally advanced rectal cancer patient treated with preoperative long-course chemoradiation.     

Extramammary Paget''s Disease Presenting on the Face

BACKGROUND: Extramammary Paget's disease is a rare neoplasm primarily affecting apocrine gland bearing skin. Although primarily affecting the anogenital area, the tumor also rarely appears in nonapocrine bearing skin and is referred as ectopic extramammary Paget's disease. OBJECTIVE: To our knowledge, we present only the second case of ectopic extramammary Paget's disease appearing on the face. METHODS: Using Mohs micrographic surgery, a rare case of ectopic extramammary Paget's disease on the face was treated in three stages. RESULTS: At 5 months there was no evidence of recurrence. CONCLUSION: Ectopic extramammary Paget's disease is a rare disease that can be effectively treated with Mohs micrographic surgery.     

Transitional cell carcinoma of the urinary tract associated with vulvar Paget's disease: a report of two cases

Two cases of the urothelial cancers associated with extramammary Paget's disease are reported. In one patient, vulvar Paget's disease was discovered 6 years after complete resection of a ureteral tumor. In another patient, vulvar and vaginal Paget's disease developed during a period of repeated transurethral surgery leading up to the final total cystectomy for recurrent bladder carcinoma. Since genital Paget's disease is frequently accompanied by internal malignancies, a skin biopsy is mandatory when an eczematous lesion has been persistent in the genital region of patients with genitourinary cancers.     

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.     

Prostatic duct adenocarcinoma with pagetoid spread on the glans penis: a case report

A 75-year-old male visited our division with asymptomatic erythema on the glans penis which he first noticed six months earlier. The patient underwent total cystoprostatectomy under the diagnosis of urothelial carcinoma of the urinary bladder four years earlier. At the time, the prostatectomy specimen incidentally revealed a prostatic acinar adenocarcinoma at the bilateral peripheral zone. A skin biopsy of the erythema revealed intraepithelial Paget's cells, and the patient underwent total penectomy under the diagnosis of extramammary Paget's disease. Histopathological examination revealed continuous intraepithelial Paget's cells from the glans penis to the urethral navicular fossa, and a ductal carcinoma was detected beneath the urethral mucosa to the excisional margin. Because the Paget's cells expressed cytokeratin 20, the tumor was diagnosed as Pagetoid spread rather than Paget's disease. Re-examination of the previous prostatectomy specimen revealed prostatic duct adenocarcinoma with prostatic acinar adenocarcinoma. Therefore, the final diagnosis was prostatic duct adenocarcinoma with Pagetoid spread to the glans penis. Follow up at nine months revealed neither local recurrence, nor distant metastases, although no adjuvant therapy has been given.     

Phase II trial of cisplatin, 5-fluorouracil,and interferon-alpha-2B as first line treatment of advanced urothelial cancer

Cisplatin based combination chemotherapy remains the mainstay for treatment of advanced urothelial cancer. The combination of 5-fluorouracil and interferon has been found to be effective second line treatment of advanced urothelial cancer. Hence, we tested the combination of cisplatin, 5-fluorouracil and interferon as first line therapy in advanced urothelial cancer. Eligible patients had to have no prior chemotherapy or interferon. Treatment consisted of cisplatin 80 mg/m(2) on day one, followed by 5-fluorouracil 750 mg/m(2) as a daily infusion for 5 days and interferon alpha 2 B 5 MU/m(2) subcutaneously daily on day 1-5 of 5-fluorouracil infusion. Cycles repeated every 21 days. Eighteen patients, of which sixteen were males were enrolled. Median age was 60 years. All patients had transitional-cell carcinoma. The median number of cycles given was 4. Thirteen patients were evaluable for response. Two patients achieved CR and 3 PR for an overall response rate of 28% (95% confidence interval 7% to 49%). Median response duration was 8.3 months. Median survival was 5.5 months. Four patients died secondary to chemotherapy toxicities. Those were GI perforation in one, bronchopneumonia in one, acute renal failure in one and one patient died at home 3 weeks following the third cycle. The above regimen demonstrates excessive toxicity and moderate activity. It cannot be recommended in its present format. Novel anti-cancer agents need to explored.     

Allelic Imbalance at p53 and Microsatellite Instability Are Predictive Markers for Resistance to Chemotherapy in Gastric Carcinoma

Background  

Combined treatment with 5-fluorouracil and cisplatin (FP chemotherapy) is an effective neoadjuvant regimen for gastric carcinoma. However, it is ineffective in half of all patients. This study tests the hypothesis that genetic markers might identify those patients with gastric cancer who would respond to neoadjuvant FP chemotherapy.     

Integration of chemotherapy in an MFD--radiotherapy plan for advanced inoperable squamous cell carcinoma of the head and neck

From January 1987 to May 1988, 16 patients with advanced squamous cell carcinoma of the head and neck received combined treatment, based on an alternating schedule of chemotherapy and multiple fractions per day (MFD)-radiotherapy. The chemotherapy regimen consisted of cisplatin, 20 mg/m2, followed by 5-fluorouracil (5-FU), 200 mg/m2 i.v. push, from days 1 to 5 during weeks 1, 5, and 9. Radiotherapy was administered in two courses of 32 Gy each (total dose, 64 Gy) during weeks 2 and 3 and 6 and 7. Each course was given in two fractions per day, 5 days per week. The 16 patients were evaluated for toxicity and response. We observed 7 complete responders, 6 partial responders, and 3 nonresponders. The overall response rate was 81%. Toxicity was heavy: 44% of the patients developed grade III-IV mucositis. Our results suggest that cisplatin and 5-fluorouracil alternating with MFD-radiotherapy is effective; however, a new less toxic scheduling must be determined.     

Successful salvage chemotherapy with gemcitabine,etoposide and cisplatin for metastatic ureteral cancer: a case report

A 35-year-old man who had undergone nephroureterectomy and a single cycle of adjuvant MVAC chemotherapy for the left ureteral cancer was referred our clinic for the treatment of paraaortic lymph node metastases. Following histologic confirmation of transitional cell carcinoma by computed tomography (CT) guided biopsy, we treated him with combination chemotherapy consisting of ifosfamide, 5-fluorouracil, etoposide and cisplatin. After 5 cycles of chemotherapy complete remission was obtained. Six months later, however, metastases recurred in the left supraclavicular and paraaortic lymph nodes. Thus, we treated him with a new combination chemotherapy comprising gemcitabine, etoposide and cisplatin which was approved as a phase I study by the institutional review board. Although he was the first patient enrolled in the study and received the minimum dose of gemcitabine (level 1), complete remission was again achieved. Adjuvant radiotherapy of 40 Gy was given to the metastatic sites. He has been well without evidence of disease for 12 months.     

Sentinel Lymph Node Biopsy in Patients with Extramammary Paget''s Disease

BACKGROUND: Patients with invasive extramammary Paget's disease appear to have a risk of regional lymph node metastasis. Despite the poor prognosis for patients with lymph node metastasis, management of extramammary Paget's disease without clinical evidence of involved nodes is controversial. OBJECTIVE: To evaluate the usefulness of sentinel lymph node biopsy, patients with extramammary Paget's disease underwent sentinel lymph node biopsy using preoperative lymphoscintigraphy and intraoperative patent blue dye injection with a handheld gamma-detecting probe. METHODS: Thirteen patients with primary genital extramammary Paget's disease were included in the study. Sentinel nodes identified were excised and examined by hematoxylin and eosin staining. All sentinel lymph nodes were also subjected to immunohistochemical staining for carcinoembryonic antigen, MUC1, cytokeratin 7, and gross cystic disease fluid protein-15. RESULTS: A total of 23 nodes were removed successfully. Tumor cells were detected in 4 nodes from four patients by hematoxylin and eosin staining. No additional lymph nodes were positive by immunohistochemistry. Three of the four sentinel-node-positive patients developed distant metastases. All nine patients without node involvement were free from disease during the follow-up period. CONCLUSION: Sentinel lymph node biopsy was safe and feasible method and may have an important role in the management of extramammary Paget's disease with clinically N0 status. To establish the optimal management of inguinal lymph nodes in extramammary Paget's disease, additional studies in large number of patients are needed.     

乳腺外佩吉特病七例报告

目的 对乳腺外佩吉特（Paget)病的临床表现、治疗方法及其预后进行分析。方法 对收治的7例乳腺外Paget病例资料进行回顾性分析。结果 3例有腹股沟淋巴结转移的患者均在5年内死亡,无腹股沟淋巴结转移者均存活。结论 乳腺外Paget病首选手术切除。一旦有淋巴结转移,其5年生存率极低。     

Development of lung metastases after curative intraperitoneal chemotherapy in a rat colon cancer model

A model of colon peritoneal carcinomatosis was developed by injecting 5 x 10(7) viable tumor cells intraperitoneally into Fisher 344 rats. All 40 control rats developed bulky abdominal tumor with ascites and died of peritoneal carcinomatosis and bowel obstruction (median survival 5 weeks). One day after tumor implantation, treatment group rats received a single intraperitoneal injection of single agent or combination chemotherapy. The most active intraperitoneal single agents were 5-fluorouracil, cisplatin, and etoposide. The most active combination was 5-fluorouracil and cisplatin. Combination chemotherapy produced a significant increase in median, 10-week, and 20-week survival (vs control and single agent). Six of 11 (55%) rats treated with intraperitoneal combination chemotherapy dying between 10-20 weeks died of lung metastasis with cure of intraperitoneal tumor. The increased ability of intraperitoneal combination chemotherapy to cure intraperitoneal disease was offset by the development of lung metastasis.     

食管癌细胞MUC1过表达对5-氟尿嘧啶及顺铂化疗效果的影响

目的探讨食管癌细胞MUC1过表达对5-氟尿嘧啶及顺铂化疗效果的影响。方法构建MUC1过表达及稳定沉默食管癌细胞株,建立食管癌细胞裸鼠移植瘤模型;顺铂（8mg／kg,d1,d7）及5-氟尿嘧啶（20mg／kg,d1～d6）腹腔注射,测量肿瘤体积及裸鼠体重,绘制生长曲线及体重曲线;计算肿瘤抑瘤率。结果顺铂与5-氟尿嘧啶均能抑制MUC1过表达食管癌移植瘤的生长,裸鼠体重及肿瘤体积与对照组比较,差异有统计学意义（P〈0．05）,且顺铂的抑制效应更明显（P〈0．05）;在MUC1稳定沉默裸鼠无明显的抑制效应。结论顺铂与5-氟尿嘧啶都能抑制MUC1过表达食管癌移植瘤的生长,顺铂的抑制效应更明显,同时对体重的影响也更明显。     

Metastatic urothelial cancer showing an efficacy by low-dose cisplatin

A 69-year-old man who had developed multiple distant metastases on retrocaval lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin, Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of 600 mg/day 5'-deoxy-5-fluorouridine (5'-DFUR), a pro-drug of 5-FU, in an outpatient setting. A partial response (62% reduction rate) was confirmed by abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in size in November 2000. Combination therapy of 5'-DFUR with low-dose CDDP could become an option for advanced bladder cancer that compromises the patient's quality of life, especially when used in an outpatient setting.     

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.     

A case of extramammary Paget's disease presenting with anuria

A 64-year-old man was admitted with dyspnea and edema of the left lower extremity to the Department of Medicine, and referred to our department presenting with anuria and scrotal edema. Physical examinations revealed a large nodular tumor extending from his penis to the lower abdomen. He was diagnosed with penile tumor that had invaded into the retroperitoneal space. Histological findings revealed extramammary Paget's disease. Radiation therapy, low dose chemotherapy, and hormone therapy were performed, but he died of invasion and multiple metastasis of the tumor 5 months later.     

EXTRAMAMMARY PAGET's DISEASE OF THE PENIS AND SCROTUM: EXCISION, RECONSTRUCTION AND EVALUATION OF OCCULT MALIGNANCY

PURPOSE: We describe treatment and reconstruction in patients after surgery for extramammary Paget's disease of the penis and scrotum. We also investigated whether this disease causes an increased risk of undiagnosed visceral malignancy. MATERIALS AND METHODS: We reviewed the databases at our institution from 1996 to 2000 and identified 6 men 67 to 87 years old (mean age 76). In addition, we reviewed the literature on the clinical and pathological features of this disease. RESULTS: In our 6 patients scrotal involvement was present in 83% and penile extramammary Paget's disease was present in 33%. Each man underwent wide local excision and large skin defects were immediately reconstructed with split-thickness skin grafts. In 1 case extramammary Paget's disease had spread to the superficial inguinal nodes. At a mean followup of 29 months there has been no local recurrence and internal malignancy has not been diagnosed. Our literature review revealed 13 patients with penoscrotal extramammary Paget's disease and visceral malignancy, including 12 (92%) with malignancy of the genitourinary system. CONCLUSIONS: Extramammary Paget's disease of the penis and scrotum is a rare disease that can be managed by excision and immediate reconstruction with skin grafting or a local skin flap. Disease may spread to the regional lymph nodes. Although genitourinary cancer may accompany penoscrotal extramammary Paget's disease, an extensive search for cancer of the thorax or abdomen may be unnecessary because only 1 reported case of colon cancer has been associated with penile or scrotal extramammary Paget's disease.