Preoperatively Irradiated Research Articles

Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer: short-term morbidity and functional outcome

Transanal endoscopic microsurgery (TEM) after radiochemotherapy (RCT) has been reported in selected cases of locally advanced rectal cancer as an alternative to traditional radical resection with total mesorectal excision with a curative intent or as diagnostic tool to confirm a pathological complete response of the primary tumor. No study has evaluated functional outcome after TEM in preoperatively irradiated patients. This study was designed to evaluate short-term morbidity (according to Clavien's classifications) and establish (by a questionnaire) continence and evacuative function after RCT and TEM, at 1 year from surgery, analyzing the impact of RCT on postoperative outcomes. Patients with locally advanced rectal cancer treated by RCT and TEM (group 1) or with early T1 or adenomas treated only by TEM (group 2) entered this cohort comparative study. Twenty-two patients entered the study as group 1 and 25 as group 2. No postoperative mortality occurred. The morbidity rate was 36.4 % in group 1 vs. 16 % in group 2 (p = 0.114). The rate of suture dehiscence was 22.7 % in group 1 vs. 4 % in group 2 (p = 0.068). No grade III complications, reoperation, or hospital readmission within 30 days was recorded in either group. One year after surgery, continence and evacuative scores in group 1 were 1.05 ± 1.25 and 24.72 ± 2.79, respectively, which were similar to group 2 (p = 0.081 and 0.288, respectively). TEM after RCT in selected rectal cancer patients has an acceptable morbidity and functional results at 1 year from surgery. Preoperative irradiation could increase postoperative short-term morbidity, but it does not seem to influence evacuative or sphincter function after 1 year from surgery.

Pathologic Radioresponse of Preoperatively Irradiated Invasive Thymomas

We have been applying preoperative radiotherapy (RT) to Masaoka stage III thymomas intending to make surgical resection more complete by reducing mass volume, to prevent possible dissemination caused by surgical manipulation and to get better survival as a result. However, the radioresponses vary from tumor to tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending on pretreatment histology. Twenty-one of stage III thymomas underwent preoperative RT plus surgery followed by postoperative RT between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO histologic criteria, resectability, long-term survival, and disease control, by preoperative RT were analyzed. Pretreatment WHO subtypes were type AB (n = 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%) decreased in size after preoperative RT with a mean (median) reduction ratio of 30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group (mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01). Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both lymphocyte and epithelial cells diminished in type B2, whereas none of the B3 tumors showed any histologic change. The values of all the cases is 90.5% in complete resection, 19.0% in no combined resection of the adjacent organs, and 77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and these value do not differ according to the WHO histologic criteria. This modality at modest doses was macroscopically and histopathologically effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma. The therapeutic benefit of preoperative RT followed by surgery and postoperative RT for stage III thymomas should be defined thoroughly.

Experiences on non-metastatic rectum tumours irradiated only preoperatively

It is an accepted fact that the local recurrence rate can be decreased up to 50% for the metastatic rectum tumours irradiated only preoperatively. 181 patients having rectum tumour were irradiated preoperatively with 36 or 40 Gy between 1990 and 2001. The classification was made according to the modified Astler-Coller pathological staging system. The radiation treatment was carried out with telecobalt unit or high energy photon of linear accelerator after computerized radiation treatment planning. The most important characterizing factor for the efficiency of the preoperative irradiation is the local recurrence rate that was found to be 21.56% in our investigation. The survival rate was significantly influenced by the age of the patient and the applied dose. Our statistical analysis was applied to investigate the efficiency of the only preoperatively irradiated patients. The results are in agreement with the reported contributions.

胸部食道癌術前照射療法後の腫よう細胞増殖能 術前非照射例との比較検討

To evaluate the influence of radiotherapy upon tumor cells from esophageal carcinoma, a cytokinetic study was made to compare those with and without pre-operative irradiation using resected specimens. In the pre-operatively irradiated group (R group), the average dosage of irradiation was 36.5±11.5 Gy, and the intervals between the end of radiotherapy and the day of surgery ranged from two to three weeks in all cases. Using paraffin-embedded materials, AgNOR numbers, a PCNA labeling index, and a positive ratio of immunohistochemical staining of ornithine decarboxylase (ODC) in tumor tissues, the R group and non-irradiated group (NR group) were examined. The non-cancerous epithelium of the non-irradiated patients were examined as well as a control (C group). Post operative survivals were assessed for clinical evaluation in stages 3 and 4 of both R and NR patients. As a result, the AgNOR numbers were 5.5±1.2 in the R, 5.6±0.8 in the NR and 2.3±0.4 in the C groups. Statistical difference was noted between the R and C groups, as well as between the NR and C groups. However, no difference was seen between the R and NR groups. PCNA L. I. was 72.6±13.8% in the R, 79.3±8.0% in the NR and 51.7±5.7% in the C groups. The statistical analysis gave the same results as the AgNOR study. The positive ratio of the ODC staining was 26.1% in the R and 48.6% in NR, whereas there was no positive in the C group. No statistical difference was seen between the R and NR groups either. Post-operative survivals of stage 3 and stage 4 patients of both the R and NR groups was almost the same.

No Demonstrated Effect of Pre-enucleation Irradiation on Survival of Patients With Uveal Melanoma

To evaluate the hypothetical effect of pre-enucleation irradiation on survival of patients with uveal melanoma. In a prospective study between 1978 and 1990, 145 patients with uveal melanoma were treated by irradiation in two fractions of 4 Gy before enucleation. A historical control group of 89 patients with uveal melanoma treated by enucleation alone was operated on between 1971 and 1990. Patients were followed up until December 1992 or until death. The mean follow-up period was 65 months in the irradiated group and 88 months in the control group. The preoperatively irradiated group of patients showed no significant improvement of the survival rate after 7 1/2 years (75.9%) compared with the control group (72.1%). Preoperative irradiation was not associated with survival (P = .93), as assessed by Cox proportional hazard analysis, adjusted for age, gender, tumor location, tumor size, cell type, and year of enucleation. Women in both the irradiated and control groups had a better prognosis than men (P = .002). Preoperative irradiation in this nonrandomized study had no effect on survival of patients with uveal melanoma.

Experience with the biofragmentable anastomotic ring (BAR) in bowel preoperatively irradiated with 6000 rad

Previous studies from the authors' laboratory using the biodegradable anastomotic ring (BAR) have demonstrated the safety of this device in animals irradiated preoperatively with the equivalent of 5000 rad; sutured, stapled, and BAR anastomoses all had leak rates of 10 percent or less in this setting. This study was undertaken to assess the safety of the BAR after irradiation with the equivalent of 6000 rad. Thirteen mongrel dogs underwent preoperative irradiation to the rectum and rectosigmoid, receiving 6000 rad according to the nominal standard dose equation. After a three-week rest period, each dog underwent anterior resection of the rectosigmoid and anastomosis with the BAR. The anastomoses were evaluated for early and late healing and anastomotic leaks. The results were compared with previous data from the authors' laboratory using an identical model. Radiographic leaks were found in 7 of 10 sutured anastomoses, 8 of 10 stapled anastomoses, and 3 of 13 BAR anastomoses (P less than 0.01). Comparative clinical leaks were 5 of 10 for sutured, 5 of 10 for stapled, and 3 of 13 for BAR anastomoses. These data suggest that the BAR may offer added safety to an anastomosis after preoperative irradiation. Whether this effect is due to the atraumatic technique of placing the device, improved blood flow to the anastomotic margins, or other factors, is still underdetermined.

Clinically resectable adenocarcinoma of the rectum treated with preoperative irradiation and surgery.

Seventy-four patients with clinically resectable adenocarcinoma of the rectum were treated with preoperative irradiation and surgery at the University of Florida between August 1975 and February 1982. All patients have been followed for at least five years. Between 1975 and 1978, 29 patients received 3500 cGy; thereafter the dose was increased to 4000 to 5000 cGy for the remaining 45 patients. All patients were treated at 180 cGy per fraction. Following preoperative irradiation, 65 of 74 patients (88 percent) underwent complete resection of their lesions. Compared with a series of historical controls treated with surgery alone, the local recurrence rate at five years was 5 of 65 (7.7 percent) vs. 39 of 135 (29 percent) (P = .001), and the five-year absolute survival was 43 of 65 (66 percent) vs. 51 of 135 (38 percent) (P less than .001). The local recurrence rate was 13 percent for patients receiving 3500 cGy and 5 percent for doses of 4000 to 5000 cGy. There was no apparent increased incidence in postoperative complications in the preoperatively irradiated patients.

Does preoperative radiation for thoracic esophageal cancer promote intramural lymphatic invasion?

Between 1976 and 1983, 43 patients with carcinoma of the thoracic esophagus underwent esophagectomy in the Department of Surgery, Tottori University. Of these 43, 22 received a total dose of 30 to 40 Gy of Co60 (2 Gy/day) preoperatively: 21 were not given preoperative irradiation treatments. The spread of intramural lymphatic cancer invasion into the esophageal wall was compared in these two groups. The preoperatively irradiated patients manifested a significantly lower rate of lymphatic cancer invasion and the depth of invasion tended to be less than in the non-irradiated patients. However, in preoperatively irradiated subjects, the horizontal cancer spread into the extra-radiation field anal to the cancer site was greater than in the other group. In addition, a significantly higher intra-abdominal lymph node metastasis rate was found in the irradiated group than in the non-irradiated group. Our findings suggest that patients with thoracic esophageal cancer who are treated with preoperative radiotherapy must be carefully monitored for the occurrence of intramural lymphatic cancer invasion and distant lymph node metastasis.

Preoperative whole pelvis versus true pelvis irradiation and/or cystectomy for bladder cancer

Between 1949 and 1974, 449 patients with bladder cancer were treated by radical cystectomy either alone (137 patients or following three preoperative radiation schemes (312 patients). True pelvis irradiation was delivered either 4000 cGy (rad) over 4 weeks in 119 patients, or 2000 cGy over 1 week in 86 patients; radical cystectomy was performed after periods averaging 6 weeks.and 2 days, respectively. Whole pelvic irradiation of 2000 cGy in 5 consecutive days was given to 107 patients who underwent cystectomy within 2 days later. Five-year survival rates for low-stage TIS-T 2 tumors of low histologic grade were 60–66% in the four treatment groups. The 5-year survival for high-stage tumors of high histologic grade, mainly in T 3 patients, was 9% in the cystectomy alone patients versus 24–32% in the preoperatively irradiated patients. The 5-year survival rates for high-stage low-grade and low-stage high-grade tumors, were 30% in the cystectomy alone group and 39–51% in the preoperative irradiation groups; the more favorable survival was noted in the whole pelvic irradiation group, which included 18% 5-year survivals for T 4 patients. Pelvic recurrence was reduced from 28% after cystectomy alone to 14–16% with true pelvis irradiation and 8% with whole pelvic irradiation. The reduced incidence of local recurrence, observed mainly in high stage or high grade tumors, was associated with tumor downstaging after irradiation. Extrapelvic metastases developed in 21–35% of the four treatment groups, underlining the inadequacy of the local radiation and surgical treatment in preventing subsequent distant spread.

Anterior resection and primary anastomosis following high dose preoperative irradiation for adenocarcinoma of the recto-sigmoid

Preoperative irradiation for adenocarcinoma of the rectum and sigmoid does not always limit the surgery to an abdominoperineal resection. From 1960 to 1976 anterior resection and primary anastomosis of the bowel has been performed in 13 patients with adenocarcinoma of the rectum and sigmoid whose tumor had been irradiated with 5000 rads with small pelvic fields. The inferior surgical resection line was within or very near the edge of the radiation field in 10 patients. In no instance was the superior resection line irradiated. Compared to a group of 79 patients treated with anterior resection only, the preoperatively irradiated patients had lower incidence of pelvic and anastomotic tumor recurrence, but a higher incidence of anastomotic leak and subsequent adhesions and intestinal obstruction. We stress that if irradiated rectum is considered for forming the anastomosis, a temporary "protective colostomy" should be strongly considered at the time of the surgery.

Preoperative Irradiation on Gastric Cancer: A Five-Year Follow-up Study

Of 202 gastric cancer cases irradiated preoperatively, 170 were followed up to evaluate irradiation effects. The resectability rate was increased by preoperative irradiation and the five-year survival rate was improved by about 15%. In every cancer stage, the five-year survival rate was higher in the irradiated than in control. Specifically, the comparative irradiated-control rates were 86% vs. 60% of cases in Stage II and 29% vs. 18% of cases in Stage III, showing significant differences at the 5% level. In cases with serosal invasion, the survival rate was particularly higher in the irradiated than in control, and the irradiated had a lower incidence of extraserosal exposure of cancer cells and were associated with markedly better prognosis than control. Cases with greater reactions in stroma besides irradiation-induced destruction of cancer cells and their nests were evidently correlated with a better prognosis. Irradiation-induced fibrosis in stroma seemed to enwrap cancer cells, reforming the “exposed” type to “non-exposed.” These factors seemed to contribute to an improved rate of resectability and better prognosis in our preoperatively irradiated gastric cancer cases.

Radiation Therapy in Cancer of the Esophagus

From 1958 to 1962, 199 cases of cancer of the esophagus were treated with radiation alone.As the recomendable technic for the middle thoracicesophagus rotating method should be taken with in conventional X-ray irradition or Co-60 teletherapy. For the upper and lower portions of the esophagus, crossfire method from 2 or 3 fields is most often undertaken.The exposure is given at the rate of 150-200 rad tumor dose daily and the total does of 5, 000-7, 000 rads in 5-7 weeks is administered in cases treated with irradiation alone.The survival rate of patients treated with irradiation alone was 29 per cent in 1 year, 9 per cent in 2 year, 6 per cent in 3 year and 5 per cent in 5 year respectively.From 1962 to 1964, 42 patients were underwent the radical resection after radical irradiation. The preoperative irradiation was administratered by tele-cobalt or Linac, and was held at 5, 000 to 6, 000 rad tumor dose during 5 to 6 weeks. The radical operation was performed between 10 and 26 day following the completion of the irradiation.Radical resection was able in 86 per cent of irradiate cases, which is much higher than 50 per cent in radical resectability of our non-irradiated cases.The survival rate of preoperatively irradiated patients was 64 per cent in 1 year, and 46 per cent in 2 Year, and it is expected that the combined treatment program will result in definitely improving five year survival rate in near future.

HISTOPATHOLOGICAL STUDIES OF THE CARCINOMA OF THE MAXILLARY SINUS WITH THE LARGE SECTIONS

Forty-seven specimens of the maxillary sinus cancer removed en bloc with the normal suround- ing tissues were observed macroscopically and his- tologically by means of large section. The sections were made in mass without sepa- rating organs or tissues of the specimens. 18 cases of those observed were preoperatively irradiated. The specimens were investigated from the points of view of the effect of the preoperative irradiation, invasion of the cell into the bone, the periost, surrounding tissues as such fatty tissues, muscles, etc. and compared with their clinical fin- dings. The results obtained were as follows. 1) 40 squamous cell carcinomas, 3 basal cell and 4 adenocarcinomas were found in the specime- ns. There was no significant relationship between their histological types and prognosis. 2) In the preoperatively non-irradiated cases, higher structural atypism, smaller alveolar struc- ture, irregularity of cellular structure and direct bony destruction by cancer cells had bad influences upon their prognosis. While in preoperatively irradiated cases, the differences in histological fin- dings were not concerned with their prognosis. 3) In many cases cancer had already destroyed the walls of the maxillary sinus, especially the na- sal wall and posterior wall (85% of the cases). 4) In 12 cases there were submaxillar lymph node metastases and in 4 cases laterocervical lymph node metastases. Their prognosis was worse than those without metastases. 5) The cases undergoing sinectomy, polypoto- my, extraction of teeth, incision of the palate be- fore adjust treatments, also had worse prognosis. In such cases histologically severe invasion into the surrounding tissues were observed. 6) Thickning of the periostal layer on the outer side of the sinus wall were observed in ma. ny cases, and those cases had good prognosis. 7) The preoperative irradiation (4000r) resul- ted into degeneration and necrosis of the cancer cell, the increase of the connective tissues thickning of the periostal layer on the outer side of the sinus wall destroyed by cancer and decrease of the can- cer in size. 18 months after the treatment 66.6% of preoperatively irradiated cases was free of recu- rrences. There were marked differences in progno- sis between the irradiated and non-irradiated cases (35.0%).