Congenital hyperinsulinism and the surgeon: lessons learned over 35 years.

BACKGROUND/PURPOSE: Congenital hyperinsulinism induces severe and unremitting hypoglycemia in newborns and infants. If poorly controlled, seizures and irreversible brain damage may result. Subtotal (<95%) or near-total (95% to 98%) pancreatectomy have been performed for glycemic control in babies who do not respond to aggressive medical therapy. Because hypoglycemia often persists after subtotal resection, 95% pancreatectomy has emerged as the procedure of choice. To define the effect of more or less extensive pancreatectomy on the management and outcome of refractory congenital hyperinsulinism, the authors examined our single institutional experience. METHODS: The records of children treated between 1963 and 1998 for congenital hyperinsulinism, and who required pancreatectomy, were reviewed. Outcome parameters included glycemic response to surgery, need for reresection, surgical morbidity, surgical and long-term mortality, and development of diabetes mellitus (DM). A complete response was defined as discharge to home on no glycemic medications, no continuous feedings, and without DM. Histological reports were reviewed and categorized as either diffuse or focal disease. RESULTS: Of 101 children treated for congenital hyperinsulinism during this period, 53 (50%) required pancreatectomy for glucose control. Mean follow-up for the study population was 9.8 +/- 1.1 years. Overall, 23 children (43%) showed a complete response, occurring in 50% of patients having > or = 95% pancreatectomy (n = 34), but in only 19% having less than 95% resection (n = 16). The remaining three babies had local excision of a solitary focal lesion, and each showed a complete response. Histopathology showed diffuse islet abnormalities in 42 specimens (79%) and solitary focal lesions in 11 (21%). A complete response was observed for 82% of focal but only 33% of diffuse lesions. Eight patients (15%) required reresection for persistent hypoglycemia, seven having diffuse lesions and one focal. Surgical morbidity occurred in 13 cases (26%), and the 30-day surgical mortality rate was 6%, each death (n = 3) occurring before 1975. DM developed in seven children (14%), each having diffuse lesions, and was independent of resection type. CONCLUSION: Because euglycemia is more readily restored, and because the risks for surgical complications and DM do not appear increased, the authors recommend 95% pancreatectomy as the initial procedure of choice for newborns and infants with congenital hyperinsulinism.

Wandering spleen: a challenging diagnosis.

Wandering spleen is rare, particularly in children, and diagnosis is difficult. It usually occurs at 20 to 40 years of age, and most cases are seen in women. Diagnosis is difficult because of lack of symptoms, unless splenic torsion has occurred. Patients usually have an asymptomatic abdominal mass, an acute abdomen, or, most commonly, a mass associated with pain. Laboratory data are nonspecific, but the diagnosis can be confirmed by imaging studies; computed tomography and duplex ultrasonography are preferred modalities. Treatment is operative because of complications of splenic infarction and possible splenectomy. Splenopexy is the treatment of choice for a noninfarcted wandering spleen. Splenectomy should be done only when there is no evidence of splenic blood flow after detorsion of the spleen. We review our experience with wandering spleen in two pediatric patients, one treated with splenopexy and the other with splenectomy.

Esophageal replacement using the colon: is it a good choice?

Thirty-eight children (2 months to 26 years of age) underwent esophageal replacement at our institution between 1962 and 1993. Twenty-four patients had esophageal atresia, with the replacement performed at a mean age of 17 months. The remaining patients (37%) had strictures and were older (mean, 7.4 years). Replacement procedures involved the right colon in 61% of cases and the transverse left colon in the others (39%). Sixty-three percent were placed substernally and 37% were done in transthoracic fashion. The average length of stay in the hospital was 34 days (range, 11 to 256 days.) Early complications (within 30 days) included cervical anastomotic leaks (11 patients; 29%) pneumonia (4), would infection (2), pneumothorax/hemothorax (3), wound dehiscence (1), prolonged ventilation (2), vocal cord paralysis (1), Horner's syndrome (1), pancreatitis (1), and perforated graft (1). Despite the incidence of early leaks, only two persisted long-term (more than 3 months). Other late complications included significant proximal strictures (5), and cologastric strictures developed in five patients. Seven cases were considered graft failures (18%), and all of these eventually require graft replacement. Additional problems included redundant graft requiring revision (4) and dumping syndrome (2). There were six cases of intestinal obstruction caused by adhesions. Four of these involved intrathoracic obstruction of the graft and two involved small bowel obstruction. There was only one death, which occurred late and was not related to the primary disease or procedure. Long-term follow-up data were available for 20 patients (53%). The follow-up period ranged from 1 to 33 years (mean, 12 years). Fourteen had excellent results after the initial interposition, being able to eat and function well without any further intervention. Seven patients (18%) have had poor results and 17 (45%) required additional procedures to obtain good functional results. In our experience, the colon continues to be a good option for esophageal replacement, but additional procedures frequently are necessary to optimize the functional outcome. Good results can be expected in the majority of cases, but late problems (ie, redundant colon and poor emptying) are not unusual, and careful follow-up is essential in the management of such patients.

Endodermal sinus tumor in children.

Malignant germ cell tumors account for about 3% of neoplasms in children, and endodermal sinus tumor (EST) is the most common histological subtype. The authors reviewed 22 years' experience (at their institution) in the management of 37 patients with this tumor. Fifteen of them (41%) had a sacrococcygeal primary, 10 had a testicular tumor (27%), 6 had an ovarian tumor (16%), 3 had a vaginal tumor (8%) and 3 had tumors at other sites (8%). Seven (19%) patients presented with metastatic disease, primarily pulmonary. The serum alpha-fetoprotein (AFP) level was elevated in all cases tested. The initial chemotherapy regimen included vincristine, actinomycin, cyclophosphamide (VAC), and Adriamycin (6 patients), but since 1985 the regimen has been changed to include cisplatin or Carboplatin, etoposide, and bleomycin (21 patients). Eight patients with testicular tumors initially were treated with surgical excision alone. Computed tomography results were a poor predictor of recurrence, but AFP surveillance was extremely sensitive. No second-look operation detected residual tumor in the absence of AFP elevation. Initial relapse for all patients tended to occur early (within 2 years), locally, and often with pulmonary metastases. Although historically the prognosis for patients with EST has been poor, the overall 2-year survival rate in this series was 70%. The best prognosis was among the children who had a testicular primary tumor (survival rate, 100%). The 2-year survival rate for patients with ovarian tumors was 67%; for those with sacrococcygeal primaries it was 60%. These results suggest that the prognosis for children with EST has improved significantly over the past decade. Contributing factors include therapy based on cisplatin, etoposide, and bleomycin, and relapse surveillance with serial AFP determinations. Second-look procedures should be reserved for patients who have an increasing level of serum AFP, suspicious computed tomography findings, and no obvious evidence of metastatic disease.

Management of the gastrointestinal tract and nutrition in patients with cloacal exstrophy.

Cloacal exstrophy is a rare condition in which there is a complex set of congenital anomalies that affect multiple-organ systems, including the gastrointestinal tract. Twenty-six patients with cloacal exstrophy have been treated at the authors' institution during the last 20 years. Gastrointestinal features usually included omphalocele, exstrophy of an everted cecal plate, a short blind-ending distal colon, imperforate anus, and, occasionally, a shortened small bowel. Additional gastrointestinal anomalies included four cases of colonic duplication, one duodenal web, and one malrotation. The average time until the initiation of enteral feeding after initial surgery was 15.6 days, and the time until discontinuation of total parenteral nutrition (TPN) was 36 days. One patient with short bowel syndrome died of TPN-associated liver failure. Five other patients exhibited short bowel physiology, but ultimately each was weaned from supplemental intravenous hyperalimentation. Four patients have undergone posterior sagittal anorectoplasty, and one has had perineal anoplasty. Of these patients, two are continent and one is free of soilage on a bowel management program. In the authors' experience with management of the gastrointestinal tract and nutrition in patients born with cloacal exstrophy, many patients initially exhibited short bowel physiology, although most eventually adapted. However, very few patients have been able to achieve bowel control.

Approach to cervicothoracic neuroblastomas via a trap-door incision.

Neuroblastomas located in the apex of the hemithorax or in the lower cervical region may make complete resection via a cervical or a thoracic approach difficult. The authors recently managed two patients with cervicothoracic neuroblastomas through an approach using the trap-door incision often applied in the setting of vascular trauma. This approach allowed a successful, complete excision of these tumors, which may have otherwise been difficult.

Meconium hydrocele in a female newborn: an unusual cause of a labial mass.

Meconium peritonitis results from in utero perforation of the bowel and subsequent spillage of meconium into the peritoneal cavity. Free communication of the peritoneal space with the processus vaginalis during gestation permits formation of a meconium hydrocele. Meconium hydrocele has been reported in the newborn scrotum but to our knowledge there has been no previous report of meconium hydrocele in the labium of a female neonate. The predominance of meconium hydrocele in the male infant may be due to the obliteration of the processus vaginalis occurring later in the male than in the female fetus.

Prevention of radiation enteritis in children, using a pelvic mesh sling.

Between 1986 and 1991, the authors used polyglycolic acid mesh slings (placed at or above the sacral promontory) in eight children with pelvic malignancies to exclude all small bowel from the pelvis during pelvic radiation therapy. The only complications of this treatment were prolonged postoperative ileus (one patient) and temporary, partial small bowel obstruction (one patient). The average amount of radiation administered to the pelvis postoperatively was 5,349 +/- 556 cGy. In one of the eight patients, gastrointestinal symptoms (diarrhea for 24 hours) developed during radiation therapy. Early radiological evaluation confirmed that the small bowel was out of the pelvis in all five of the patients studied. Mesh disruption occurred between 2 and 5 months postoperatively (mean, 3.4 +/- 1.5 months) and was often identified symptomatically by the patient. Seven of the eight survived, with disease remission in six. Pelvic disease was absent at the time of death in the one patient who did not survive. Throughout the follow-up period (mean, 20 months) no survivor has had delayed symptoms of radiation enteritis. In children with pelvic malignancies in whom aggressive application of pelvic irradiation is required, the use of an absorbable pelvic mesh sling appears efficacious in preventing radiation-associated enteritis.

Partial splenectomy: the preferred alternative for the treatment of splenic cysts.

We report six pediatric patients who had a partial splenectomy for splenic cysts and a seventh patient who had a total splenectomy. There were six epidermoid cysts and one traumatic cyst. All patients had benign postoperative courses. All patients who underwent partial splenectomy had a significant postoperative rise in platelet count that subsequently returned toward baseline. This rise implies a loss of splenic function, although the exact meaning of this is unclear. All patients had late postoperative liver-spleen scans that showed mean spleen size and function to be normal. We have described several methods of partial splenectomy used at Children's Hospital of Philadelphia. Recommendations for patients undergoing partial splenectomy include preoperative pneumococcus and Hemophilus influenzae vaccinations and prophylactic antibiotics postoperatively. The antibiotics are terminated if a liver-spleen scan and platelet count at the end of 3 months' time are normal.

Surgical experience with thirteen conjoined twins.

Conjoined twins occur in approximately one in 50,000 or so births, and most do not survive. The authors report herein their experience with 13 conjoined twins over the last 30 years, involving those of the following forms: thoracopagus (4 cases), omphalopagus (1 case), ischiopagus (4 cases), pygopagus (1 case), craniopagus (1 case), and incomplete or parasitic varieties (2 cases). The various diagnostic and imaging studies used are described in detail for each form of twinning. Separation is best delayed until such infants are relatively mature (i.e., 6-12 months of age). Operative survival was 50% in those operated on in the neonatal period, but 90% in those over 4 months of age. Ten separations were attempted in 13 sets of twins, with 16 operative survivors. Significantly, up to 10 years after surgery, there were six late deaths due to serious associated congenital anomalies, predominantly cardiac. Improved recent survival is probably the result of the availability of more accurate imaging studies and better anesthetic and operative techniques, with great emphasis on performing immediate reconstruction whenever possible. Use of skin expanders and prosthetic mesh has facilitated wound closure. In the future, ex vivo cardiac reconstruction and autotransplantation may permit separation of twins with complicated conjoined hearts.

The usefulness of open-lung biopsy in the pediatric bone marrow transplant population.

From October 1976 to October 1986, 126 children had bone marrow transplants at the Children's Hospital of Philadelphia. The indications were acute lymphocytic leukemia (ALL) (30), nonlymphocytic leukemia (24), aplastic anemia (15), solid tumors (47), and miscellaneous conditions (10). Of these, 21 (17%) underwent 22 open-lung biopsies. Fourteen of these patients showed no causative microorganism. When a cause was found it was viral (usually cytomegalovirus [CMV]) in three, fungal in one, Pneumocystis carinii alone in two, both viral and pneumocystis in one, and a combination of viral, bacterial, and pneumocystis in one. Thirteen patients died due to continued deterioration after the biopsy. In only two patients was there a significant change in antimicrobial therapy as a result of the biopsy. Both had Pneumocystis (one in combination with virus and bacteria). One patient with chronic infiltrates showed a lymphocytic interstitial pneumonia, which responded well to steroids. Open-lung biopsy is currently of limited value in this patient population. Survival is dismal unless the patient has Pneumocystis. We believe that prospective studies should be set up to compare open-lung biopsy with empiric antimicrobial therapy. A major emphasis must be on prevention.

Resection with primary anastomosis for necrotizing enterocolitis: a contrasting view.

Resection with primary anastomosis is currently being advocated for treatment of infants with necrotizing enterocolitis. To determine whether our own data would support such an approach, we reviewed retrospectively our experience with this disease since 1974. Since that time, 173 infants have been admitted for treatment of advanced (surgical) disease in its acute phase, of whom 143 underwent resection for cure; the remainder either underwent laparotomy with decompression (3), laparotomy with drainage (3), laparotomy alone (14), died at operation (1), or could not be resuscitated sufficiently to withstand operation (9). Excluded were patients who underwent operative repair of late stricture (6), all of whom survived with no morbidity. Among those resected for cure, 27 infants were carefully selected by the operating surgeon for treatment by means of resection with primary anastomosis, based on the limited and apparently discrete nature of their disease; in three the procedure was combined with a decompressing enterostomy. In the majority of cases (14), the disease was found to involve multiple areas of intestine, but was limited to a particular anatomic region, usually distal ileum and/or ascending colon; in the remainder, it was due to discrete ileal or jejunal perforation or ulcer. Overall survival among those resected for cure was 65% (96/143). It was 48% (13/27) among those treated by means of resection with primary anastomosis but 72% (83/116) among those who underwent resection with enterostomy. However, if the early years of the series (1974 to 1976) are excluded, a time when resection with enterostomy had not yet become established as standard therapy, overall survival was 77% (77/100), 64% (9/14) among those anastomosed primarily.

Omphalocele, cryptorchidism, and brain malformations.

Nineteen male infants died with a large omphalocele and 52% had associated cryptorchidism. However, two different groups with both omphalocele and cryptorchidism were recognized: (1) Eleven patients with omphalocele without brain malformation and an incidence of undescended testes not significantly different from the normal population; (2) Eight patients with omphalocele and brain malformation all having cryptorchidism. A comparison of the groups indicated that intact intraabdominal pressure during intrauterine life is not a main driving force of testicular descent, whereas normal testicular descent may occur only when the brain is normally developed. Whenever a child with omphalocele and cryptorchidism is examined, careful evaluation of the central nervous system is indicated. This triad of malformations may have prognostic and therapeutic implications.

Posterior sagittal exposure for reconstructive surgery for cloacal anomalies.

We treated seven girls with a cloacal anomaly through a posterior sagittal exposure. Six patients, aged 5 months to 2 1/2 years, underwent a primary reconstructive operation with urethroplasty, vaginoplasty, and posterior sagittal anorectoplasty as a single procedure. All had undergone diverting sigmoid colostomies as newborns, four had previous vesicostomies, and one had a vaginostomy. The seventh girl, a 9-year-old, had undergone a number of attempts at reconstruction. All underwent endoscopy and contrast studies of the cloaca before definitive reconstruction. This preoperative evaluation gave necessary information regarding the length and caliber of the cloacal channel and the level of confluence of the urinary, genital, and intestinal tracts. However, major decisions regarding reconstruction were often possible only in the operating room. To construct a neoanus with optimal sphincteric control, all seven underwent posterior sagittal anorectoplasty. Two required laparotomies to mobilize additional colonic length. Three developed urethrovaginal fistulae after repair. Critical decisions regarding urethral and vaginal reconstruction depend on the findings at cystoscopy and operation. The posterior sagittal approach gives excellent exposure for these decisions and the subsequent reconstruction of three functioning perineal orifices.

Massive gastrointestinal hemorrhage in children with posterior fossa tumors.

Over a 12-month period (September 1984 to September 1985), 64 children with newly diagnosed brain tumors were admitted to the Neurosurgical Service at The Children's Hospital of Philadelphia. Of these children, 29 had posterior fossa tumors. Of this population of children with posterior fossa tumors, three patients aged 4 months, 22 months, and 4 years old developed massive exsanguinating upper gastrointestinal hemorrhage within seven days of their primary neurosurgical procedure. In each instance, large posterior duodenal ulcers were encountered and were treated with oversewing of the duodenal ulcer and vagotomy-pyloroplasty. Follow-up currently ranges from 18 to 26 months. All three children have survived and none have had any gastrointestinal bleeding since then. Massive exsanguinating hemorrhage was not seen in children with brain tumors in locations other than the posterior fossa. In this population of patients, we advocate the use of prophylactic cimetidine and titration of gastric acidity with antacids.

Microdiverticulitis: a rare but distinct cause of small bowel obstruction in early infancy.

During a 20-year period, eight term infants admitted to a large children's hospital for treatment of dehydration associated with diarrhea (6) and vomiting (2), and who ranged in age from 10 to 60 days at onset of symptoms and 18 to 75 days at presentation, developed distal small bowel obstruction following apparently successful rehydration. With the exception of a single infant who was dead on arrival, and another whose obstruction went unrecognized, all infants came to operation shortly after obstruction was confirmed. In each case, a severely inflamed area of distal ileum (7) or proximal colon (1) was found at autopsy (2) or operation (6) to be the cause; perforation was present in four of the cases. Resection of the diseased segments of intestine, and primary anastomosis, were performed in all six operated cases; reoperation was required in four of the six for leaks (3) and adhesions (1). All but two survived. Pathologically, the resected intestinal segments showed a unique pattern of injury: numerous punctate ulcers were apparent, which undermined the muscularis mucosae, without evidence of necrosis. Regenerating epithelium extended through these defects, resulting in the presence of glandular invaginations, which were surrounded by a brisk inflammatory response: hence the term "microdiverticulitis." We believe this lesion represents a beginning or furtive attempt at repair of severely inflamed, but viable intestine, and that it is a rare but true cause of small bowel obstruction in early infancy, separate and distinct from necrotizing enterocolitis.

Recent experience with choledochal cyst.

This report details an 11-year experience with 17 patients ranging from newborn to 17 years with choledochal cyst. Two distinct groups were noted: an infantile group (mean age: 3 months) with obstructive jaundice identical to biliary atresia and a late onset group (mean age: 9 years) with various combinations of pain, mass, and jaundice. Two patients had cystoduodenostomy performed and both required revision. One of six patients who had Roux-Y cystojejunostomy required revision. All seven patients who had primary cyst excision and two patients who had secondary cyst excision with Roux-Y hepaticojejunostomy have been followed prospectively and have done well. The follow-up period ranges from 1-11 years with an average of 5.8 years. Cyst excision should be performed as a primary or secondary procedure whenever feasible. The rare patients with intrahepatic ductal dilatation (Caroli's disease) are best approached by hepatic lobectomy when possible, and those with choledochocele should be treated by unroofing the cyst as indicated by the anatomy encountered.

Malignant ovarian tumors in children and adolescents.

Eighteen patients aged 4 to 18 years (median, 10 years) were treated at the Children's Cancer Research Center of The Children's Hospital of Philadelphia (CHP) from September 1973 to September 1983 for malignant ovarian tumors. The pathologic categories were endodermal sinus tumor (eight patients), embryonal carcinoma (three patients), pure dysgerminoma (three patients), adenocarcinoma (three patients), and malignant granulosa-cell tumor (one patient). In 1973 and 1975, respectively, two patients with endodermal sinus tumors were treated with surgical removal with or without radiation therapy (RT) and chemotherapy with vincristine (Vc) and actinomycin D+ cyclophosphamide + Adriamycin (Adria Laboratories, Columbus, OH) (ACAdr); both developed local recurrence within 12 months and died of tumor. Since 1977, four of six patients with endodermal sinus tumors have been managed successfully with surgery followed by chemotherapy with cisplatin (P), bleomycin (B), vinblastine (Vb), and ACAdr; none received RT. One died of recurrent tumor and the other died of congestive heart failure attributed to Adriamycin (Adr). All three patients with embryonal carcinoma were well after surgical excision alone (one patient) or surgery and chemotherapy with cisplatin + bleomycin + vinblastine (PBVb) + ACAdr (two patients). Treatment of the remaining seven patients included excision alone (two patients) or excision and chemotherapy (five patients) with various combinations of Vc, ACAdr, and P. One patient with granulosa-theca cell tumor also received whole abdominal RT (3000 rad by external beam), and died of congestive heart failure attributed to Adr. The other six children were free of detectable tumor 16 months to 8 years from diagnosis. Chemotherapy with PBVb and actinomycin D + cyclophosphamide (AC) should be used in the postoperative management of young persons with malignant ovarian tumors. Adr is of doubtful value and may be considerably toxic. RT is of limited use and usually is not indicated.