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Introduction

Early gastrointestinal complications of radiotherapy for pelvic lesions are quite common and usually pres-ent no problem in their recognition and differentiation from either delayed effects of irradiation or recurrence of malignancy ( Requarth and Roberts20 and Anderson, Witkowski and Pontius2). These early complications are characterized by acute inflammation, tenesmus, pain, bleeding and diarrhea, ordinarily occurring within a few weeks to a month following completion of x-ray therapy. Commonly, the symptoms subside within a few months. However, delayed irradiation damage, such as the de-velopment of fecal fistulas and intestinal obstruction, may occur many years following completion of radiation therapy for malignant disease of the pelvis. Craig and Buie9 report a series of 200 cases of irradia-tion proctitis following xray therapy for carcinoma of the cervix. In their series symptoms occurred in 43% of the cases within one month, 27% developed symptoms in one to six months and 16% of the cases developed symptoms following a period of one year. The remain-ing 14% of the cases manitested symptoms: several years from the completion of treatment, with one case having a delayed interval of seven years.

In one case an ileovesical and ileoileal fistula devel-oped 14 years following irradiation for carcinoma of the cervix. These fistulas resulted in longstanding morbid-ity and prostration. Following surgical correction of the fistulas, rapid improvement and weight gain occurred (Simpson and Spaulding25 ). Late complications of ra-

diotherapy are therefore less well known and more fre-quently confused with recurrent carcinoma. In a series of 621 cases irradiated for carcinoma of the cervix, the chief complications were obstructive phenomena, main-ly due to adhesive fibrous bands. Proctitis and recto-vaginal and vesicovaginal fistulas were also frequently encountered.18 Hoffman14 reported on eight cases of stenosis of the ileum following irradiation for carcinoma of the uterine cervix and the successful surgical correc-tion by resection of the diseased segment In addition he reported on five cases of ureteral stenosis, many years following irradiation for carcinoma of the cervix and the uterine body, with successful treatment by means of free inplantation of the ureter after resection of the stenotic segment, utilizing an end-to-end anastomosis. Perkins and Sput19 discussed nine cases of irradiation stenosis of the rectosigmoid and transverse colon. The histologic findings were characterized by obliterative vasculitis with subendothelial foam cell deposits, lead-ing to ischemic changes with riecrosis of the wall and subsequent perforation. The finding of subendothelial swelling, fibrosis and foam cell deposition within small caliber arteries ‘and arterioles leading to stenosis with subsequent necrosis and fibrosis of the affected organs has been recognized by numerous investigators as the basic cause lot the irradiation ulcer and other types of ir-radiation injury, in particular, the delayed type of irradia-tion damage. 12,22,24,29,31,32

That fibrosis is indeed very important, in producing shrinkage of the length of the bowel segment is shown by Spratt et al26 in experimental studies in dogs. From an, exteriorized 5 cm long small bowel segment exposed to 4,000 rads. in one sitting, only a string of scar tissue of 2 mm length remained eight months following irradia-tion. Brick3 in a series of 100 cases concluded that the maximum safe level for the stomach and bowel is 4,000 roentgens and for the colon 4,500 roentgens. Brown dif-ferentiates the delayed effects of irradiation, which are often and quite understandably confused with a recur-rence of tumor, from the immediate irradiation effects,

Fatal Gastrointestinal ComplicationsFollowing Cobalt Therapy

for Carcinoma Of theUterine Cervix

Arno Albert Roscher, M.D., F.I.C.s., F.A.S.C.P., F.A.C.P.,* and John S. Woodard, M.D.**

Granada Hills, California

*Director of Laboratories, Granada Hills Community Hospital and Clinical Asst. Professor of Pathology, University of California Irvine, California College of Medicine, Los Angeles.** Clinical Asst. Professor of Pathology, University of Southern California and University of California Irvine, California College of Medicine, Los Angeles.

This paper accepted for publication December 12, 1968.First published in INTERNATIONAL SURGERY, June 1969, Vol 51, No. 6

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such as tenesmus, proctitis, bloody stools and diarrhea. These delayed changes comprise bowel obstruction, fe-cal fistulas, and fibrous bands. In most instances the ob-struction is secondary to incarceration rather than to ste-nosis of the lumen. There is also progressive vascular obliteration of the small caliber vessels. Those patients have often a conspicuously “frozen pelvis,” and there-fore often give an impression of having a recurrence of tumor. Surgery for any reason in those cases increases the incidence of morbidity (Robinson21). Although morbidity following irradiationis quite com-mon, mortality is a rather uncommon complication and has been reported only twice following relatively small dosages of x-rays, leading to small bowel necrosis after 1,500 roentgens (Cathie6).· It is the purpose of this paper to report a case where increased individual susceptibility to irradiation with a fatal outcome followed full dose ir-radiation therapy for carcinoma of the cervix subsequent to hysterectomy:

Report of a Case

In March 1959, a 35-year-old white housewife underwent a total hysterectomy because of carcinoma of the cervix. The specimen revealed extensive residual intraepithelial squamous cell carcinoma of the cervix with an area of microinvasion (Fig. 1). Postoperatively the patient had a course of cobalt radiation therapy. She received 4,000 roentgens anteriorly and 3,500 roentgens posteriorly, using a total of four portals over a period of six weeks. This treatment was tolerated well.

In April 1961, more than two years, after the operation and irradiation, she complained of left lower quadrant pains. In June she complained of epigastric pain with occasional episodes of vomiting. By July she had lost

five pounds, had bloody stools and her complaints had become more severe. Because of the persistence of bloody stools, an exploratory laparotomy was per-formed. At operation there was an area of necrosis and fibrosis involving approximately eight inches of the lower ileum. This segment of small bowel, was resected and an anastomosis was made between the ileum and the ascending colon, leaving a blind segment of terminal il-eum in place. A side-to-side colostomy anastomosis of the sigmoid was performed because of a stenotic and fibrotic segment in the lower portion. An external fecal fistula developed near the anastomosis, but drainage from it gradually diminished. In August, however, the fecal fistula recurred, leading to additional abdominal surgery after continuous draining of the fistula for one month. The fistula was resected and a colostomy stoma was constructed using the lowest remaining portion of the descending colon. In March 1962, having gained eight pounds since her preceding surgery, she was readmitted for the purpose of resecting all involved segments of small and large bowel and reconstruction of the continuity of the gastro-intestinal tract. The previously bypassed small atrophic terminal ileum was resected along with the adjacent ce-cum and ascending colon up to the previous ileocolic anastomosis. There was marked fibrous reaction of all the tissue in the pelvis making dissection difficult. The upper rectosigmoid and part of the’ descending colon were resected with an anastomosis performed between the descending colon and the rectum in order to rees-tablish the continuity of the intestinal tract and enable her to have normal bowel movements. Shortly thereafter a fecal fistula developed between the site of the anasto-mosis and the suprapubic region. In May repair of the fe-cal fistula was attempted. Dihiscence of the coloproctic anastomosis was found and a diverting ileostomy was made. From October 23 to October 29, 1962, she was hospitalized because of weakness, carpopedal spasm and other musculoskeletal signs. On admission her hematocrit was 40%, hemoglobin 13 gm%, white cell count 23,700/cu mm, BUN 43%, phos-phorus 7.2 mg%, potassium 6.7 mEq/l, calcium 3.9 mEq/l, sodium 132 mEq/l, chloride 72 mEq/l and CO2 combining power was 25 mEq/1. She improved after having received several blood transfusions as well as intravenous fluids, calcium, high caloric diet and symp-tomatic treatment. Two days later she was readmitted because of dehydra-tion, weight loss, continued vomiting, muscle cramps and an episode of unconsciousness when she was found at home with mucus exuding from her mouth and with a

Fig. 1. — Left. Cervix with extensive residual in situ carcinoma ( H. & E. 100x). Right. Cervix with microinvasion (H. & E. 450x).

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blood pressure of 80/40 mm of mercury. She again re-ceived intravenous fluids, calcium and other therapy, but continued to vomit and to be extremely weak and unable to care for herself.

On this admission her hematocrit had been 45%, WBC 8,700, serum potassium 2.9 mEq/1, sodium 144 mEq/1, chloride 98 mEq/1 and C02 18 mEq/1. The serum cal-cium was 4.0 mEq/1 and phosphorus 1.7 mg%. On October 13th the BUN had been 42%, the serum phosphorus 3.6 mg%, albumin 3.1 gm and globulin 4.6 gm%. The calcium on repeat examination was 4.6 mEq/l and magnesium 1.0 mg% (serum magnesium normal level is 1.5-2.5 mg%). Urine calcium was 0.025 mEq/l, urine sodium was 0.75 mEq/l and the urine potassium 32.5 mEq/l. She weighed only 70 lbs at this time. She was treated with massive volumes of plasma intrave-nously as well as electrolytes, including sodium, potas-sium, calcium and magnesium. Between November 12 and her discharge on November 24, her intake and out-put were recorded and she was weighed daily. At dis-charge her weight was 77.5 lbs. The vomiting and nau-sea had disappeared. She was eating and drinking well, walking around and felt much stronger. Fluid intake had varied from three to nine liters. The output from the il-eostomy varied between 5000 and 9000 cc for 24 hours. The BUN had fallen to 17 mg% and her serum creatinine was 0.5 mg%. An interesting aspect of the case was the comparative electrolyte and nitrogen concentrations in the ileostomy fluid, the urine and the blood. Her urine output averaged only 180-200 cc per day during the last ten days of hos-pitalization. The initial urine sodium concentration was 0.75 mEq/l (the serum sodium was 132 mEq/l ) thus showing that the renal tubules reabsorbed sodium very effectively. The ileostomy fluid sodium varied from 20-55 mEq/l and the potassium averaged 20 mEq/l. The ileostomy fluid also contained 20 mEq/l of urea nitrogen, 20 mg% of creatinine and 25 mg of uric acid. These amounts varied considerably in several specimens tak-en at several times. About three weeks after being dismissed she was seen at her home in shock and barely conscious. At this time she was transferred to another hospital where she was admitted to a renal electrolyte clinic. She returned to this hospital clinic twice because the doctors intended to re-establish the continuity of her intestinal tract. However, on February 5, 1963 she again had suffered severe nau-sea and vomiting for three days and was in shock. She was hospitalized, received massive infusions of plasma and electrolytes and water balance was reestablished.

Attempts to diminish the volume discharged from the il-eostomy by means of various drugs were unsuccessful. At this time she was placed on a gluten free diet be-cause she developed a nontropical sprue syndrome. She became hypotensive on several occasions but was rescued each time by the administration of blood and plasma, restoring it to a normal level. The attending sur-geon found it impossible to reestablish the continuity of the intestinal tract owing to unhealed areas in the sig-moid colon, evident on proctoscopy. In the course of her hospitalization she did not improve, lost hope of recovery and requested on several occasions that all treatment be discontinued. A progress note on February 17 stated that all therapeutic efforts had been ineffective. On the 18th the patient was again found in shock and requested to be left alone when arrangements were made to treat her. She expired on the same day.

Autopsy Findings

The body was that of a middle-aged and extremely ema-ciated white female. Externally nothing remarkable was noted on the head, neck, chest or extremities. The abdo-men was flat. There were numerous midabdominal scars from previously performed surgeries. There was a pat-ent ileostomy stoma in the left lower quadrant. The sto-ma was moist, edematous and moderately hemorrhagic, but the lumen was patent. Internally nothing remarkable was noted within the neck region. The heart and lungs were essentially normal. The abdomen contained no free fluid. There were numerous dense adhesions be-tween the abdominal wall and the small bowel loops and remaining large bowel. There was surgical absence of the terminal ileum, proximal portion of the ascend-ing colon and sigmoid colon with adjacent portions of the descending colon and rectum, as well as the uterus and adnexae. Dense adhesions between the pelvic floor and the urinary bladder were also observed. Around the sacrum and promontory, dense fibrous layers were ob-served which fused with the root of the mesentery. Most of the small bowel loops were thick-walled and had a pipe-stem consistency. There was no lymphadenopathy and no gross evidence of tumor recurrence. The liver, spleen and pancreas as well as the esophagus, stom-ach and duodenum appeared essentially normal.

Microscopic Findings The cardiorespiratory system revealed no abnormali-ties. The liver, spleen, pancreas, stomach, esophagus and duodenum were essentially within normal limits. Significant changes, however, were apparent on mi-

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Fig. 2. — Left. Bowel with denuded mucosaand submucosa inflammatory infiltrates. ( H. & E. 100x).

Fig 3. — Right.Subserosal ans perivascularfibrosis and narrowing of the vessel lumen. ( H. & E. 100x).

Fig. 4.— Left. Subendothelial fibrosis of the cap-ilary with severe stenosis of the lumen. ( H. & E. 450x).

Fig 5.— Right. Vessel with severe subendothe-lial fibrosis and foam cell deposits. ( H. & E. 450x).

Fig 6.— Left. Submucosal space with fibrosis showing a stenosing arteriole and dialated capil-laries. ( H. & E. 100x).

Fig 7.— Right. Submucosal space with irradia-tion fibroblast. ( H. & E. 1000x oil immersion).

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croscopic section of the remainder of the lower intes-tinal tract. The serosal surfaces revealed large fibrous tags and extensive fibrosis of the entire wall of some sections. There was extensive fibrous matting of many loops. The fibrotic process extended in areas through all the layers of the individual bowel sections, result-ing in complete obliteration of the submucosal space, muscularis and capillaries. The overlying mucosa was in many regions denuded and in other areas ulcerated and heavily infiltrated by inflammatory cells (Fig. 2). In other sections there was perivascular fibrosis, as well as extensive narrowing of the small vascular channels of the serosa and other portions of the gut wall (Fig. 3). The major changes of the vessels were within the subendo-thelial space. There were large areas of fibrosis leading in many regions to partial or almost complete stenosis of the lumina (Fig. 4). Other sections revealed foam cell deposits within the subendothelial space (Fig. 5). Some of the larger vascular channels showed fragmentation of the elastic lamellae and the internal elastica. Special stains, including trichrome stain and Van Cieson elastic stain, demonstrated marked fibrosis of the subendothe-lial space, leading in many areas to complete oblitera-tion of the existing vascular channels. Some areas were encountered in which both hypertrophied and stenotic vascular channels alternated with capillaries showing dilatation of their lumina and heavy engorgement with erythrocytes (Fig. 6). The submucosal space revealed dense fibrosis with an occasional giant radiation fibro-blast (Fig. 7).

Discussion The case presented supports the concept that the indi-vidual susceptibility of patients may vary considerably in regards to their reaction to the injurious effects of ir-radiation. In general, dosages of 4000-5000 roentgens are well tolerated. This has been in particular stressed by Kottmeier and Gray15 and Hoffman.14 The delayed gastrointestinal complications following irradiation thera-py are primarily those of bowel obstruction, either of the rectosigmoid colon or of the ileum, and fistula formation, especially between the rectum and the vagina (Todd27). The complications are normally of a localized nature and are due to fibrosis, obliterative arteritis, atrophy and ne-crosis, all of which may follow intensive radiation of tis-sues regardless of location and be dependent upon the nature of the tissue irradiated. The onset of symptoms may occur at any time, from several months after the completion of treatment to many years. It is difficult to explain the pathogenesis of a fibrotic stricture or fistula which appears 10, 15 or even 25 years after complete healing of an acute inflammatory radiation reaction. It is

probably due to a combination of decreased tissue re-serve available for repair and reduced circulation, viabil-ity and nutrition. Other injurious effects such as inflam-mation and bacterial action are certainly contributing factors. It is interesting that in some cases a fecal fistula will close if a successful diversion of the fecal stream is accomplish able by a colostomy or ileostomy. The time element, however, is apparently important since months are often required to make a fistula close. In many in-stances bowel obstruction occurs due to incarceration behind adhesive bands which formed as a consequence of irradiation. The delayed complications follow intrinsic, as well as extrinsic irradiation, either from radium appli-cation through the vagina or external radiation therapy utilizing cobalt or x-ray treatment. In many of those treat-ed, a frozen pelvis results, giving the impression of tu-mor recurrence. The differential diagnosis is often quite difficult and cannot be solved until death has ensued.I,5,10,16,30 The presented case illustrates an increased susceptibility of the individual to irradiation, resulting in an extensive degree of fibrosis, fecal fistula and inability of the tissues to heal, therefore making surgical correc-tion of the fecal fistula difficult or impossible. Surgery in previously irradiated tissues is followed by an extensive degree of morbidity as well as mortality (Robinson21). In many cases after successful resection of a stenotic segment secondary to irradiation, complete recovery will result.14 In other cases, and in particular in this one, dif-ferent bowel loops are affected, even if they are distant from the area of irradiation. The resulting complications, secondary to metabolic disturbances, mainly of nutri-tion, water and electrolytes, are stressed by the hospital course of the patient. It is well accepted that the delayed effects of irradiation relate to occlusive vascular phenom-ena and subsequent fibrosis. This case illustrates, how-ever, that metabolic disturbances leading to sprue like symptoms may characterize, somewhat, late as well as early complications. Such metabolic irradiation changes may relate to depolymerization of mucopolysaccharides and connective tissue ground substances which lead to defective absorption of nutritional essentials such as glucose, thionine and pyridoxine. The decrease in these substances leads to edema and increased capillary permeability. Other important changes are destruction of mitochondria and other cell components as well as nuclei. These changes can be produced by 3000 rads. The reduced absorption is directly related to a reduc-tion or absence of mitochondria. Other factors relating to decreased absorption in the early as well as the late phases of the radiation syndrome are the disruption and degranulation of the mast cells with release· of hepa-rin, histamine and 5-hydroxy-tryptamine. The latter two lead to the formation of leaks in the endothelium of small blood vessels.11

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Studies carried out with high resolution autoradiography after administration of thymidine, labelled with radioac-tive tritium, on the gastrointestinal epithelium of previ-ously irradiated animals, showed reduction of DNA syn-thesis directly proportional to the amount of irradiation delivered. These changes are seen with doses as low as 200 rads.13

Micromolecular changes can be demonstrated electro-microscopically in the mucosal villi secured by biopsy by means of Crosby’s sound. The biopsies were done in patients suffering from carcinoma of the cervix and con-sequently irradiated with small doses. After 100 rads. the authors noticed the presence of large-sized granules of dishomogenous structure which are not seen in normal mucosa. The authors tentatively submit the hypothesis that the granular formations probably represent different metabolic conditions in the structure which make up the enzymatic patrimony of the cells.28

Comment

The presented case illustrates a patient who succumbed two and a half years later to the effects of bowel compli-cations after radiation therapy for microinvasive carcino-ma of the uterine cervix. Following a two and a half year interval essentially free of complications, she developed signs and symptoms suggestive of bowel obstructions, possibly due to recurrence of the tumor.

The autopsy revealed no evidence of recurrence of tu-mor in any of the sections and the most striking features were severe fibrosis of the entire wall of the individual bowel loops and ischemic ulcerations of the mucosa at many points. Fecal fistulas were found which were also the result of ischemia and subsequent necrosis of the tissues. The smaller vascular channels and the ar-terioles were significantly involved and showed striking narrowing of their lumina secondary to subendothelial fi-brosis and foam cell deposits with stenosis. The remain-ing portions of the bowel wall were in areas completely fibrotic and matted with the surrounding tissues. The case stresses the difference in individual susceptibility to irradiation as well as the poor wound healing and the increased hazards of surgery in previously irradiated tis-sues,21 It is to be anticipated that as methods of irradia-tion treatment improve and more accurate dosimetry is developed and also when better knowledge is gained of cancer and radiation biology, the incidence of those complications will continue to decline as it has in the past.7 Utilization of irradiation treatment in the control of malignant disease of the abdominal or pelvic organs has always been associated with some injury to the gastroin-

testinal tract in a small proportion of patients. The use of irradiation treatment is a double edged sword which will result in injury to the surrounding normal tissues. This must be accepted as a calculated risk, therefore irradia-tion therapy should be used very judiciously and only with very strict indication. Some authors have estimated the incidence of gastrointestinal complications for pel-vic irradiation to be from 1% to 17% (Brown4). These figures, however, can only be of relative value because of differences in techniques, differences in evaluating the degree of injury and the heterogeneity of the patient population. The actual incidence of complications which will result in permanently disabling conditions requiring surgical intervention is approximately in the order of 2% (Brown4). Gastrointestinal complications attributed to ir-radiation have most frequently followed the application of intracavitary radium therapy in treatment of cancer of the uterine cervix or uterus. The problem is an increas-ing one because of the increased availability of radiation therapy operating at super voltage levels.10,16

There is apparently a considerable degree of unex-plained variability and susceptibility of the response of the individual patient to irradiation therapy. Also the in-cidence and the variety of complications as well as the effectiveness of tumor control appear to he in general related to time-dose-volume relationships. In this regard the larger the total dose or the volume irradiated or the more rapidly the treatment is delivered, the more promi-nent will be the gastrointestinal complications.30

The gastrointestinal tract has irradiation sensitivities second only to that of the bone marrow (DesJardins10). The small intestine is in particular susceptible to radia-tion injury compared to the colon, but is ordinarily less frequently the site of complications in the clinical prac-tice, because of the fact that the small bowel is a less fixed organ than the colon. Fixed daily portals or radium placements used in radiation therapy will expose a given loop of small bowel less frequently to irradiation than is the case with the large bowel and only a fraction of the total dose applied will strike the small bowel. On the other hand, in patients who have had previous abdomi-nal or pelvic surgery or a combination of irradiation and surgery, loops of small bowel may become immobilized by adhesions and therefore receive the total delivered dosage. In those patients, a much higher incidence of ir-radiation complications involving morbidity and mortality of the small intestine is to be anticipated (Conrad8 and McIntosh and Hutton17).

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Summary The paper presents a case of microinvasive carcinoma of the uterine cervix, treated with a combination of sur-gery followed by a full course of tumor dose irradiation. The postirradiation complications, the difference of in-dividual susceptibility, as well as the strict indication for irradiation are stressed. The course of events strongly suggests that in cases of in situ carcinoma of the uter-ine cervix, even with microinvasion, surgery alone would be more beneficial to the patient than a combination of surgery and irradiation. since such treatment seems to have much greater morbiditv and mortality than surgery alone. On the other hand. in cases of advanced carcino-ma of the pelvic region, irradiation certainly is indicated, since at this stage the development of delayed irradia-tion damage will trail the inevitable course of advanced pelvix carcinoma. Zusammenfassung Es wird ein Fall von mikroinvasivem Krebs des Gebär-mutterhalses bescprochen, der mit e,iner Kombination von Chirurgie und nachfolgender Bestrahlung behan-delt wurde. Die Komplikationen nach Bestrahlung, die Unterschiede individueller Strahlenempfindlichkeit und die Notwendigkeit strenger Indikationen zur Bestrahlung werden hervorgehoben. Der Ablauf der Dinge deutet stark darauf hin, dass in Fällen von Gebärmutterhalskar-zinom in situ sogar mit Mikroinvasion die chirurgische Entfernung als solche der Kombination von Bestrahlung und Chirurgie vorzuziehen ist, da die kombinierte Be-handlung eine grössere Morbidität und Mortalität auf-weist. Andererseits ist in Fällen von vorgeschrittenem Krebs des Beckens die Bestrahlung indiziert, da hier die Entwicklung von Spätfolgen der Bestrahlung erst nach dem unvermeidlichen Kurs vorgeschrittener Krebser-krankung zu erwarten wäre.

Riassunto Questo lavoro presenta un caso di microinvasione carcinoma tosa del cervice uterino, trattato con una combinazione di chirurgia e seguito d’un pieno corso d’irradiazione per que sto genere di tumore. Le com-plicazioni post-irradiaziorii, le differenze di suscettibilita individuale, ed in addizione anche le direzioni per le pro-prie indicazioni dei casi scelti per l’irradiazione, sono, propriamente descritti. Il corso degli eventi clinici suggeriscono fortemente che nei casi di carcinoma in situ del cervice uterino, come nei casi di micro-invasione, il procedimento chirur-

gico da solo sarebbe più vantagiosó al paziente che una combinazione di chirurgia ed irradiazione, poichè tale combinazione di trattamento pare d’avere una più grande morbidità e mortalità, che nei casi trattati sola-mente con il procedimento chirurgico. D’altra parte, nei casi di carcinoma avanzato della regione pelvica, irradi-azione è certamente ed altamente indicata, poichè in questo stadio il posponimento d’irrauiazione il processo neoplastico continuerà d’invadere e seguire l’inevitabile corso d’invasione di carcinoma della pelvi.

Resumen Se preseIita una caso de carcinoma microinvasor del cuello uterino, tratado mediante cirugía y dosis total de irradiación. Se enfatizanlas complicaciones post-irradi-ación, diferencias en tolerancia a la misma, e indicacio-nes, estrictas. La experiencia sugiere en forma determi-nante que en los casos de carcinoma in situ del cuello uterino, aún con microinvasión, la cirugía por sí sola es de más beneficio que el tratamiento combinado, debido a que tél último presenta mayor morbilidad y mortalidad. Por el contrario, en casos avanzados del area pélvica, la irradiación debe utilizarse, ya que durante este estadío los efectos secundarios pueden ser menores a los de un carcinoma pélvico avanzádo.

Sumário O presente trabalho apresenta um caso de microcar-cinôma invasívo do cólo uteríno que foi tratado por um processo combinado de cirurgía seguida de um curso completo de irradiação. São expressadas as complica-ções post-irradiação, as diferenças da susceptibilidade individual, bem como as indicações estritas da irradia-ção. O curso dos eventos firmemente sugerem que em casos de carcinôma “in situ” do cólo úteríno mesmo com microinvasão, a cirurgía isoladamente pode ser mais benêfica para a paciente do que a combinação da cirurgíá’ e a irradiação, desde que tal tratamento parece ter urna morbididade e mortalidade maior que a cirurgía isoladamente. De outro lado, em casos de carcinôma avançados da região pélvica, a irradiação certamente é indicada, desde que neste estágio dedesenvolvimento dos danos tardíos da irradiação seguirão inevitavel-mente o curso do carcinôma pélvico avançado.

References

1. Aldridge, A. H.: Intestinal Injuries Resulting from Irradiation Treatment of Uterine Carcinoma. Am. J. Obst. Cynec. 44:833,

1942. 2. Anderson, R. E.; Witkowski, L. J., and Pontius, C. V.: Radiation

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Stricture of the Small Intestine. Surgery 38:605, 1955. 3. Brick, 1. B.: Effects of Million Volt Irradiation on Gastro-intestinal Tract. Arch. Int. Med. 96: 26-31, 1955. 4. Brown, F. A.: Gastro-intestinal Complications Associated with Irradiation Therapy Characteritic, Confusing and Compounded.

Am. J. Dig. Dis. 7:1006-1025, 1962. 5. Buie, L. A., and Malmgren, C. A.: Factitial Proctitis. A Justifiable

Lesion Observed in Patients Following Irradiation. J. Internat. Clin. 3:68, 1930.

6. Cathie, 1. A. B.: Ulceration of Small Intestine Following Irradiation of Pelvis. Am. J. Roent-genol. 39:895-898, 1938.

7. Chau, P. M.; Fletcher, C. H.; Rutledge, F. N., and Dodd, C. D. J.: Complications in High Dose Whole Pelvis Irradiation in Female Pelvic Can-cer. Am. J. Roentgenol. 87:22, 1962.

8. Conrad, R. A.: Some Effects of Ionizing Radiation on the Physiol-ogy of the Gastro-intestinal Tract: A Review. Radiation Res. 5:167, 1957.

9. Craig, M. S., and Buie, L. A.: Factitial Irradiation Proctitis: Clinical Pathological Study of 200 Cases. Surgery 25:472-487, 1949.

10. Des Jardins, A. U.: Action of Roentgen Rays and Radium on the Gastro-intestinal Tract. Am. J. Roentgenol. 26:337, 1931.

11. Detrick, L. E.: Mucopolysaccharides in Post-irradiation Intestinal Absorption Studies. Ann. N.Y. Acad. Sci. 106:636-645.

12. Cassman, A.: Zur Histologie des Roentgenulcers. Fortschr. Rontgenstr. 2:199-207, 1899. 13. Cuastier, H.: Sherman, F. C.; Becker, C., and Cronkite, E. D.: Cell

Renewal, Maturation and Decay in Gastro-intestinal Epithelia of Normal and Irradiated Animals. Proc. Second United Nations Intern. Conf. Peaceful Uses of Atomic Energy, Ceneva 22:22, 1958.

14. Hoffman, V.: Strahlen Schaden der Harnwege. Munch. Med. Wschr. 5:2485-2488, 1962.

15. Kottmeier, H. L., and Cray, M. C.: Rectal and Bladder Injuries in Relation to Irradiation Dosage in Carcinoma of the Cervix. Am. J. Obst. Cynec. 82:72, 1962.

16. Leucutia, T.: Late Reactions Following ,Super Voltage Radiation Therapy. Am. J. Roentgenol. 82:721, 1959.

17. McIntosh, H. C., and Hutton, J. E.: Clinical and Roentgen Aspects of Irradiation and Stricture of the Rectum and Sigmoid. Am. J. Roentgenol. 52:647, 1942.

18. Morton, D. C., and Kerner, J. A.: Reactions to X-ray and Radium Therapy in the Treatment of Cancer of the Uterine Cervix. Am. J. Obst. Cynec. 57:625-636, 1949.

19. Perkins, D. E., and Sput, H. J.: Intestinal Stenosis Following Radiation Therapy. Am. J. Radiol. 88:953-966, 1962.

20. Requarth, W., and Roberts, S.: Intestina: Injuries Following Irradiation of Pelvic Viscera for Malignancy. Arch. Surg. 73:682,

1956. 21. Robinson, D. W.: The Hazards of Surgery in Irradiated Tissues.

Arch. Surg. 71:410-418, 1955. 22. Roscher, A. A.; Steele, B. C., and Woodard, J. S.: Carotid Artery

Rupture After Irradiation of Larynx for Carcinoma. Arch. Otolar-yngol. 83:472-476, 1966.

23. Roscher, A. A., et al: Carotid Artery Rupture After Irradiation of Larynx. J.A.M.A. 196:237, 1966.

24. Sheehan, J. E.: Foam Cell Plaques in Intima of Irradiated Small Arteries of 100-500 Microns in Diameter. Arch. Path. 37:297-303, 1944.

25. Simpson, W. J., and Spaulding, W. B.: Long Delayed Bowel Complications of Radiotherapy. Canad. M. A. J. 80:810-812,

1959. 26. Spratt, J. S., Jr.; Heinbecker, D., and Saltzstein, S. L.: Influence of Succinyl-Sulfathiozole (Sulfasu-

zadine-Merck), Upon Response of Canine Small Intestine to Irradiation. Cancer 14:862-874, 1964.

27. Todd, T. F.: Rectal Ulceration Following Irradiation Treatment of Carcinoma of Cervix Uteri:

Pseudo carcinoma of the Rectum. Surg., Cynec. & Obst. 67:617, 1938.

28. Torri, C., and Casbarrini, C.: Alterations of the Microscopic Structures of the Human Intestinal Mucosa Irradiated by Means of Small Doses of X-rays. Radiol. Clin. 32:47-56, 1963.

29. Warren, S.: Effects of Radiation on Normal Tissues. Arch. Path. 34:1070-1084, 1942.

30. Wigby, P. E.: Post Irradiation Stricture of Rectum and Sigmoid Colon Following Treatment for Cervical Cancer. Am. J.

Roentgenol. 49:307, 1943. 31. Windholz, F.: Zur Kenntnis der Blutgefassver-anderungen in

Rontgenbestrahlten Cewebe. Strahlentherapie 59:662-670, 1937.

32. Wohlbach, S. B.: The Pathologic Histology of Chronic X-ray Der-matitis and Early X-ray Carcinoma. J. Med. Res. 21:415-449, 1909.