Kinji Nishiyama

Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers

The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. the epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P < 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes.

Treatment of carcinoma of the uterine cervix by remotely controlled afterloading intracavitary radiotherapy with high-dose rate: a comparative study with a low-dose rate system

From September, 1974 through December, 1979, a total of 249 patients with carcinoma of the cervix uteri Stage IIb and III were randomly allocated to either remotely controlled high-dose-rate intracavitary radiotherapy or manual afterloading low-dose-rate therapy, with radiotherapy of 20 Gy in 2 weeks to Point A to whole pelvis and 40 Gy in 4 weeks to the parametria. The dose to Point A by intracavitary radiotherapy was 40-60 Gy with one or two fractions in the low-dose-rate group and 30 Gy for the high-dose-rate group by 3 fractions with a once a week schedule. The purpose of this paper is to compare the results between the groups and to clarify the problems in the high-dose-rate group clinically. The local control rate was higher in the high-dose-rate group; however, the complication rate was also higher in this group than in the low-dose-rate group. The dose schedule and the place of rectal dose measurement is discussed. The overall cumulative survival rate was nearly the same in both groups (55% at 5 years), although some difference was noted in each stage. The most common cause of death was distant metastasis outside the pelvis and the second most common was intercurrent disease in Stage IIb and local failure in Stage III.

Feasibility and Efficacy of Combination Therapy With Preoperative Full-Dose Gemcitabine, Concurrent Three-Dimensional Conformal Radiation, Surgery, and Postoperative Liver Perfusion Chemotherapy for T3-Pancreatic Cancer

Objective:To evaluate both the feasibility and efficacy of our combined therapy, which consisted of preoperative chemoradiation, surgery, and postoperative liver perfusion chemotherapy (LPC) for patients with T3 (extended beyond the pancreatic confines) cancer of the pancreas. Summary Background Data:Because of the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of T3-pancreatic cancer are extremely poor. Methods:During the period from 2002 to 2007, 38 patients with T3-pancreatic cancers consented to receive a combination of preoperative chemoradiation, surgery, and postoperative LPC. With the aid of 3D radiation planning, irradiation fields were constructed that included both the primary pancreatic tumor and retropancreatic tissues while taking care to exclude any section of the gastrointestinal tract. The total dose of radiation was 50 Gy (2 Gy × 25 fractions/5 weeks) and was administered in combination with gemcitabine treatments (1000 mg/m2/week × 9/3 months). Preoperative restaging via computerized tomography and intraoperative inspection were used to determine if pancreatectomy was indicated. For respected cases, one catheter was placed into the gastroduodenal artery and another one into the superior mesenteric vein. Postoperatively, 5-FU (125 mg/day × 28 days) was infused via each of these 2 routes. Results:Preoperative chemoradiation was completed for all 38 patients, including 3 patients who required gemcitabine-dose reduction. Seven patients (18%) did not undergo surgical resection because either distant metastases or progressive local tumors had been detected after chemoradiation. The remaining 31 patients (82%) underwent pancreatectomy plus postoperative LPC, without postoperative or in-hospital mortality. The 5-year survival rate after pancreatectomy was 53%, with low incidences of both local recurrence (9%) and liver metastasis (7%). Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) for 30 patients (96%) and negative nodal involvement for 28 patients (90%). Conclusion:Results of this trial suggest that a combination of preoperative full-dose gemcitabine, concurrent 3D-conformal radiation, surgery, and postoperative LPC is feasible for the treatment of T3-pancreatic cancer. Using the method described in this article, we were able to effectively reduce the incidence of both local and liver recurrence. Therefore, this type of combination therapy seems promising for improving long-term outcomes for patients with T3-cancers of the pancreas. This study is registered with University hospital Medical information Network clinical trials Registry number, UMIN000001804.

A prospective analysis of subacute thyroid dysfunction after neck irradiation

PURPOSE Exposure of the thyroid to therapeutic doses of external irradiation has been demonstrated to induce thyroid dysfunction. This study was designed to assess the relationship between irradiation and early thyroid dysfunction, prospectively. METHODS AND MATERIALS Twenty patients in whom the thyroid was incidentally exposed to therapeutic doses of irradiation were studied. The dose given to the thyroid was 40-54 Gy over 4-7 weeks. Thyroid function tests, including serum thyroid stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), antithyroglobulin antibody, and antimicrosomal antibody, were performed prior to irradiation and at 3, 6, and 12 months after radiotherapy. RESULTS Serum TSH levels did not change significantly at 3 months after irradiation (mean TSH level: 1.33 microU/ml before irradiation, 1.74 microU/ml at 3 months, p = 0.11). However, a significant elevation was noted at 6 months (mean TSH: 3.50 microU/ml at 6 months, p = 0.0001, vs. preirradiation), when TSH levels were higher than preirradiation levels in 19 of 20 patients. After irradiation, 13 patients remained in a euthyroid state (euthyroid group), while in the other 7 patients hypothyroidism occurred (hypothyroid group) and thyroid hormone-replacement therapy was performed. After 6 months, elevation of TSH was less significant in the euthyroid group, whereas elevation of TSH persisted continuously and exponentially in the hypothyroid group. Thyroid autoantibodies did not turn positive in any patient during follow-up. CONCLUSIONS Damage of the thyroid develops in most patients when the organ is exposed to radiation. This radiation-induced damage is initially manifested within 6 months after irradiation.

Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

PURPOSE To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. METHODS AND MATERIALS Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. RESULTS Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. CONCLUSION Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

ACUTE RADIATION THYROIDITIS

PURPOSE Radiation-induced thyroid dysfunction is considered a late effect. We prospectively assessed acute reactions of the thyroid to external neck irradiation. METHODS AND MATERIALS This study included 22 patients in whom the thyroid was incidentally exposed to therapeutic doses of radiation. Thyroid function tests included measurements of serum thyroid stimulating hormone (TSH), free and total triiodothyronine (T3) and thyroxine (T4), thyroglobulin, and antithyroid antibodies. These tests were performed before radiotherapy (baseline values), after approximately 40 Gy had been administrated, 2 weeks after the end of radiotherapy, and 3 and 6 months after the beginning of radiotherapy. RESULTS Mean serum levels of TSH were 1.53, 0.55, 0.78, 2.14, and 7.57 microU/ml before radiotherapy, after 40 Gy irradiation, 2 weeks after the end of radiotherapy, and 3 and 6 months after radiotherapy, respectively. Thus, levels of TSH exhibited two phases: a significant decrease during radiotherapy (thyrotoxic phase) and an increase after radiotherapy (hypothyroid phase) (baseline vs. 40 Gy: p < 0.0001, baseline vs. 6 months: p = 0.003). Increases of thyroid hormones were subtle during radiotherapy. CONCLUSIONS We believe that radiation promotes release of excessive amounts of thyroid hormones during radiotherapy owing to suppression of TSH secretion. In addition to the late damage (hypothyroidism), thyrotoxicosis occurs when the thyroid gland receives a therapeutic doses of external radiation.

Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma

BACKGROUND Pancreatic fistula (PF) is a common complication after pancreatectomy. Previous reports indicate that preoperative irradiation decreases the risk of PF after pancreatoduodenectomy. In this context, the impact of preoperative chemoradiation therapy (CRT) on PF formation after distal pancreatectomy is of interest. METHODS Fifty-eight patients with pancreatic adenocarcinoma who underwent distal pancreatectomy, including 28 patients with preoperative gemcitabine-based CRT and 30 patients without preoperative treatment, were assessed in this study. The incidence and severity of postoperative PF, assessed according to the definition of the International Study Group on Pancreatic Fistula, were compared between the 2 groups. RESULTS In the CRT group, 86% of patients did not develop PF, whereas grades A and B PF were observed in 1 and 3 patients, respectively. In the non-CRT group, 33% of patients did not develop a PF, whereas grades A and B PF were observed in 9 and 11 patients, respectively. The incidence of clinically significant PF, defined as either grade B or grade C PF, was less in the CRT group (P = .031). The amylase activities in the draining fluid on postoperative days 1 and 3 were both less in the CRT group (P = .003 and P = .006, respectively). CONCLUSION Preoperative CRT significantly decreases the incidence of PF after distal pancreatectomy, which potentially provides another benefit to patients in addition to its original advantages (ie, locoregional effect and patient selection effect), allowing more opportunities for the immediate initiation of postoperative adjuvant treatment.

Computed tomographic findings of nasopharyngeal carcinoma with skull base and intracranial involvement

Twenty‐nine patients with nasopharyngeal carcinoma (NPC) with skull base or intracranial involvement were analyzed by high‐resolution computed tomography (CT). We divided the path of the primary tumor spread into six directions from the nasopharynx. The most common direction of spread was the anterior region, and the second most common was the posterolateral region. Recently, high resolution CT has been used for the diagnosis of the nasopharynx. T‐staging of NPC was made according to the International Union Against Cancer (UICC) TNM classification system, depending on clinical findings and conventional radiograph examinations (not including CT). CT images were valuable for detection of the primary tumor involvement of the skull base region in NPC. Furthermore, bone target CT images were better for searching for subtle bony changes. Therefore, we recommend that CT should be used in T‐staging of NPC systematically. When CT is used as one of the staging criteria, some patients with NPC with subtle bony changes will be upstaged.

Concurrent chemoradiotherapy for advanced pancreatic cancer: 1,000 mg/m2 gemcitabine can be administered using limited-field radiotherapy.

Purpose:To examine the feasibility of concurrent use of full-dose gemcitabine (GEM) and radiotherapy for advanced pancreatic cancer.Patient and Methods:22 patients with advanced pancreatic cancer were subjected to concurrent chemoradiotherapy (GEM 1,000 mg/m2 weekly, three times during 4 weeks). They received limited-field irradiation by three-dimensional radiotherapy planning.Results:Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation and at least three times concurrent administration of 1 g/m2 GEM). One patient with unresectable tail cancer showed peritonitis carcinomatosa and both chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of GEM was necessary in another four patients. In addition, radiotherapy was discontinued in one patient for fatigue. Grade 3 hematologic toxicity was detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia) in one patient (5%). In total, the response rate amounted to 32% (seven partial responses), and the median survival time (MST) was 16 months. Among the twelve patients who received preoperative chemoradiotherapy, nine underwent surgery and showed a survival rate of 78% at 1 year. Another 13 patients without surgery showed 14 months of MST. No regional lymph node failure has appeared so far.Conclusion:Limited-field radiotherapy enables the safe concurrent administration of 1,000 mg/m2 GEM.Ziel:Untersuchung der Durchführbarkeit einer simultanen Verabreichung von Gemcitabin (GEM) in voller Dosis und Radiotherapie bei fortgeschrittenem Pankreaskarzinom.Patienten und Methodik:22 Patienten mit fortgeschrittenem Pankreaskarzinom wurden mit simultaner Radiochemotherapie (GEM 1 000 mg/m2 wöchentlich, dreimal während 4 Wochen) behandelt. Sie erhielten eine begrenzte Bestrahlung auf der Basis einer dreidimensionalen konformen Radiotherapie-Planung.Ergebnisse:16 der 22 Patienten (72%) schlossen die Behandlung ab (50 Gy Bestrahlung und simultane Verabreichung von mindestens dreimal 1 g/m2 GEM). Ein Patient mit irresektablem Pankreasschwanzkarzinom wies eine Peritonitis carcinomatosa auf, und sowohl die Chemo- als auch die Radiotherapie mussten abgebrochen werden. Bei vier weiteren Patienten wurde eine Dosisverringerung oder Auslassung von GEM notwendig. Darüber hinaus wurde die Radiotherapie bei einem Patienten wegen Erschöpfung abgebrochen. Eine hämatologische Toxizität Grad 3 wurde bei acht (36%) und eine nichthämatologische Toxizität Grad 3 (Anorexie) bei einem Patienten (5%) beobachtet. Die Ansprechrate betrug insgesamt 32% (siebenmal partielles Ansprechen) und die mediane Überlebenszeit (MST) 16 Monate. Von den zwölf Patienten, die sich einer präoperativen Radiochemotherapie unterzogen, wurden neun operiert; diese Patienten wiesen nach 1 Jahr eine Überlebensrate von 78% auf. Bei den 13 Patienten ohne operativen Eingriff ergab sich eine MST von 14 Monaten. Bisher ist es zu keinem Ausfall der regionären Lymphknotenfunktion gekommen.Schlussfolgerung:Eine begrenzte Radiotherapie ermöglicht die sichere simultane Verabreichung von 1 000 mg/m2 GEM.

Concurrent Chemoradiotherapy for Advanced Pancreatic Cancer

Purpose:To examine the feasibility of concurrent use of full-dose gemcitabine (GEM) and radiotherapy for advanced pancreatic cancer.Patient and Methods:22 patients with advanced pancreatic cancer were subjected to concurrent chemoradiotherapy (GEM 1,000 mg/m2 weekly, three times during 4 weeks). They received limited-field irradiation by three-dimensional radiotherapy planning.Results:Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation and at least three times concurrent administration of 1 g/m2 GEM). One patient with unresectable tail cancer showed peritonitis carcinomatosa and both chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of GEM was necessary in another four patients. In addition, radiotherapy was discontinued in one patient for fatigue. Grade 3 hematologic toxicity was detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia) in one patient (5%). In total, the response rate amounted to 32% (seven partial responses), and the median survival time (MST) was 16 months. Among the twelve patients who received preoperative chemoradiotherapy, nine underwent surgery and showed a survival rate of 78% at 1 year. Another 13 patients without surgery showed 14 months of MST. No regional lymph node failure has appeared so far.Conclusion:Limited-field radiotherapy enables the safe concurrent administration of 1,000 mg/m2 GEM.Ziel:Untersuchung der Durchführbarkeit einer simultanen Verabreichung von Gemcitabin (GEM) in voller Dosis und Radiotherapie bei fortgeschrittenem Pankreaskarzinom.Patienten und Methodik:22 Patienten mit fortgeschrittenem Pankreaskarzinom wurden mit simultaner Radiochemotherapie (GEM 1 000 mg/m2 wöchentlich, dreimal während 4 Wochen) behandelt. Sie erhielten eine begrenzte Bestrahlung auf der Basis einer dreidimensionalen konformen Radiotherapie-Planung.Ergebnisse:16 der 22 Patienten (72%) schlossen die Behandlung ab (50 Gy Bestrahlung und simultane Verabreichung von mindestens dreimal 1 g/m2 GEM). Ein Patient mit irresektablem Pankreasschwanzkarzinom wies eine Peritonitis carcinomatosa auf, und sowohl die Chemo- als auch die Radiotherapie mussten abgebrochen werden. Bei vier weiteren Patienten wurde eine Dosisverringerung oder Auslassung von GEM notwendig. Darüber hinaus wurde die Radiotherapie bei einem Patienten wegen Erschöpfung abgebrochen. Eine hämatologische Toxizität Grad 3 wurde bei acht (36%) und eine nichthämatologische Toxizität Grad 3 (Anorexie) bei einem Patienten (5%) beobachtet. Die Ansprechrate betrug insgesamt 32% (siebenmal partielles Ansprechen) und die mediane Überlebenszeit (MST) 16 Monate. Von den zwölf Patienten, die sich einer präoperativen Radiochemotherapie unterzogen, wurden neun operiert; diese Patienten wiesen nach 1 Jahr eine Überlebensrate von 78% auf. Bei den 13 Patienten ohne operativen Eingriff ergab sich eine MST von 14 Monaten. Bisher ist es zu keinem Ausfall der regionären Lymphknotenfunktion gekommen.Schlussfolgerung:Eine begrenzte Radiotherapie ermöglicht die sichere simultane Verabreichung von 1 000 mg/m2 GEM.