Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis.

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma.

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500-5000 rad in 180-200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180-200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (192Ir) to a dose of 2000-2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500-2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5 1/2, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6-23 months). Four of the 5 patients received a transcatheter 192Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone +/- 5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter 192Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.

Surgical treatment of pancreatitis: review of a series.

In this review of the surgical experience with pancreatitis, 55 patients had acute relapsing pancreatitis associated with gallstones and 47 had chronic pancreatitis of alcoholic, idiopathic, or familial causation. The severity of pancreatitis associated with gallstones could not be correlated with results of preoperative biochemical tests; only one-third of patients were found to have stones within the biliary ductal system; and postoperative mortality (5%) could not be correlated with the severity of pancreatic inflammation or the timing of surgical intervention. Postoperative observations have revealed that all but four of the patients have remained asymptomatic. With regard to the patients with alcoholic, idiopathic, or familial disease who had significant pancreatic ductal dilatation or obstruction, ductal drainage procedures with or without resection benefited 80%. In the absence of ductal dilatation or obstruction, major resective surgery benefited 50% of patients. Continuing alcohol abuse limited the effectiveness of any operative procedure, and diabetes occurred more often after major resective procedures.

Mass lesions of the liver.

Each of the six most common mass lesions of the liver may vary with respect to pathogenesis, clinical manifestations, natural history, usefulness of diagnostic tests, and the need for and value of surgical treatment. Despite these many variables, one broad generalization can be made: three lesions (cysts, cavernous hemangiomas, and focal nodular hyperplasia) usually are incidental findings that can be ignored, whereas three other tumors (adenomas, malignant hepatomas, and metastatic lesions) involve a threat to life that may be modified by surgical removal. This generalization, however, is not a guide to specific management because exceptions, atypical manifestations, diagnostic difficulties, and variations in the risks and limitations of surgical therapy are so common. The widespread use of new techniques for "imaging" has changed the responsibility of both the medical and the surgical hepatologist. Lessons of the past learned from the management of clinically evident symptomatic lesions have little usefulness in the management of small, "early," or indeterminate lesions. In these circumstances, physicians, surgeons, and radiologists must work in concert when a lesion is first found. Only then will clinically relevant tests be done that will ensure proper treatment of the patient.

Hepatobiliary cancer--surgical considerations.

Most cancers of the hepatobiliary system will have grown beyond the limits of curative resection by the time they become clinically evident. This reality has fostered therapeutic nihilism, and most physicians and surgeons in their pessimism have failed to study the early modes of spread of these tumors--patterns of growth that are relevant to proper treatment of those patients who do have lesions that can be removed with hope of achieving a cure. Moreover, anatomic and technical complexities may beget surgical reluctance in the management of potentially curable lesions. Therefore, this review is offered for orientation and perspective for those who would hope to offer optimal treatment for patients who have primary cancers of the liver, gallbladder, or biliary ducts. The review includes considerations of (1) surgical anatomy, (2) modes of spread, (3) assessment of resectability, (4) surgical technique, and (5) results of operative treatment in relation to "curative" resection. Also offered are some guides to palliative surgical management of tumors that have reached the hepatic hilus.

Radical pancreatoduodenectomy--a procedure to be abandoned?

Radical pancreatoduodenectomy, or Whipple's procedure, has gradually fallen into disrepute during the past decade. This loss of popularity has resulted from excessive postoperative mortality and morbidity due to inherent technical difficulties, the dismal long-term survival when the procedure is done for adenocarcinoma of the pancreas, and the current enthusiasm for total pancreatectomy. Our objective was to assess the technical aspects of the Whipple procedure as they relate to subsequent morbidity and mortality. Conclusions are drawn from the evaluation of 146 consecutive patients who underwent this procedure between 1970 and 1979 for either benign (10 patients) or malignant (136 patients) diseases of the pancreas and periampullary region. The postoperative mortality was 4.1%. Significant morbidity occurred in 34% of patients, and early reoperation was required in 7.5% of these patients. The median postoperative hospital stay was 19 days. The relatively low postoperative mortality indicates that inherent technical difficulties of the Whipple procedure can be overcome and supports its continued use in carefully selected patients. The persistent high morbidity and the rather poor long-term results following treatment of certain pancreatic malignancies place individual surgical judgment and technical expertise at a premium when ever this classic operation is contemplated.

Proximal gastric vagotomy. Initial experience.

Proximal gastric vagotomy was performed in 223 patients with chronic duodenal ulceration between 1973 and 1977. The follow-up ranged from 6 to 78 months with a mean of 39 months. There was no operative mortality. Adverse postoperative sequelae, including delayed gastric emptying, dumping, diarrhea, and reflux gastritis, were seen in less than 3% of patients. Ulcers recurred in 11 patients (4.9%). We conclude that proximal gastric vagotomy is an effective, safe, and satisfactory operation for chronic duodenal ulcer over the short term.

Clinical trial of adjuvant chemotherapy after surgical resection of colorectal cancer metastatic to the liver.

Adjuvant chemotherapy consisting of 5-fluorouracil and semustine was given to 26 patients who had undergone resection (with curative intent) of hepatic metastatic lesions from a primary colorectal carcinoma. Our objective was to obtain preliminary observations regarding the effectiveness of this regimen for improving the long-term survival associated with hepatic resection alone in these patients (the overall 5-year survival after hepatic resection is 25% at our institution). At the time of analysis, the malignant disease had progressed in 19 of our patients, and 17 patients had died. For all patients who receive adjuvant chemotherapy, the median duration of survival is 34 months, and the estimated 5-year survival is 15%. Statistical analysis indicated no significant advantage in survival for the study patients in comparison with 26 control patients who were treated with hepatic resection only and were closely matched for prognostic factors. Because 5-fluorouracil plus semustine conferred no apparent beneficial effects as an adjuvant treatment in this exploratory study, we do not recommend a definitive randomized trial of this regimen.

Is proximal pancreatoduodenectomy with pyloric preservation superior to total pancreatectomy?

The records of all patients who underwent pylorus-preserving pancreatic resection (29 subtotal and 4 total pancreatectomies) during a 10-year period at the Mayo Clinic were reviewed. Thirty-day operative mortality was 6%. Early postoperative morbidity occurred in 45% of patients and necessitated reoperation in four patients. One patient had a hemorrhage from a marginal ulcer in the early postoperative period. The incidence of late postoperative morbidity was 18%. Marginal ulcers developed in the late postoperative period in three additional patients, for an overall incidence of 13%. One patient underwent vagotomy and pyloroplasty because of intractable bleeding 2 years after initial operation. The 29 patients who underwent pylorus-preserving pancreatoduodenectomy (PPW) were compared (retrospectively) with 200 patients who had undergone standard pancreatoduodenectomy (Whipple operation) during the same 10-year period. The overall incidences of marginal ulcer were 10% in the PPW group and 5% in the Whipple group; the incidences of delayed gastric emptying were similar in these groups. We believe that caution is warranted in the use of PPW, as yet an unproved procedure.

Choledochal cysts in adults: clinical management.

The surgical management of 29 adults with choledochal cysts is reviewed with emphasis on clinicopathologic features, long-term postoperative results (mean 9.1 years), and factors affecting outcome. Clinical symptoms were characterized by abdominal pain, jaundice, and cholangitis. Coexistent hepatobiliary pathologic findings were more complex and frequent than those that occur in children and included cystolithiasis or cholelithiasis, pancreatitis, malignancy, cirrhosis with portal hypertension, and intrahepatic abscess. Associated pathologic findings and cyst type (type I-22, II-1, III-2, IVA-4) determined the operative approach. In patients with type I or IVA cysts, results of cyst excision were excellent in five of seven patients but results of cystenterostomy were excellent in only seven of 19 patients. The high prevalence of pancreatitis (33%) and cyst-associated malignancy (28%) were major causes of treatment failure. Cyst excision with Roux-en-Y hepaticojejunostomy is recommended as the treatment of choice for adults to eliminate pancreatitis by pancreaticobiliary disconnection and possibly to reduce the risk of malignancy.

Primary hepatic malignancy: surgical management and determinants of survival.

To further define the clinicopathologic features and determinants of survival, we reviewed the cases of 110 patients with primary hepatic malignancy managed surgically between 1975 and 1986. Presenting signs of symptoms were pain (57%), fatigue (48%), abdominal mass (40%), and weight loss (33%). Twenty-six percent of patients had a history of hepatitis or cirrhosis. Histopathologically, tumors were hepatocarcinoma (72%), fibrolamellar variant (7%), cholangiocarcinoma (9%), mixed (7%), and other (5%). Resectability rate with curative intention was 67%. Exploration and biopsy alone was performed in 27% and palliative resection in 6%. Hospital mortality was 9%, and serious morbidity was 22%. Perioperative morbidity and mortality were significantly associated with operative blood loss. Median survival was 12.6 months, with a 5-year survival of 18%. Median survival after curative resection was 22.8 months, and 5-year survival was 27%. Univariate analysis showed that female sex, normal performance status, well-differentiated tumor, and curative resection were associated with increased survival; cholangiocarcinoma, nodal metastases, cirrhosis, hypocalcemia, prolonged prothrombin time, and increased serum transaminase and alkaline phosphatase were associated with decreased survival. Cox multivariate analysis showed that curative resection, normal performance status, and well-differentiated tumors were associated with increased survival, and prolonged prothrombin time and hypocalcemia were associated with decreased survival.

Prognostic significance of nuclear deoxyribonucleic acid ploidy patterns in resected hepatic metastases from colorectal carcinoma.

Nuclear deoxyribonucleic acid (DNA) ploidy studies of paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 101 surgically resected hepatic metastases from colorectal cancer. In 28 patients, the corresponding primary carcinoma of the metastases was also studied. Tumor clinicopathology and clinical course of the patients were reviewed. Preparation of paraffin-embedded tissue specimens was performed by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindelov et al. Eighty-eight of 101 metastatic tumors and 26 of 28 primary tumors yielded evaluable DNA histograms. Twenty-six metastases showed a DNA diploid pattern, 25 showed a significantly increased 4C peak (DNA tetraploid/polyploid), and 37 had a DNA aneuploid peak. Ploidy pattern was constant between primary and metastases in 84.6% of tumors. No significant relationship between host and tumor characteristics and ploidy pattern was found except for a correlation between grade 3 metastases and DNA aneuploid. Survival of patients with DNA aneuploid metastases was significantly less than that of patients with DNA diploid metastases (p = 0.03). However, among DNA nondiploid metastases, survival was significantly less for low DNA index metastases (less than or equal to 1.5) than for high DNA index (greater than 1.5) metastases (p less than 0.05). Flow cytometric DNA ploidy measurements may have prognostic value for patients with resected hepatic metastases from colorectal carcinoma.

Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence.

The Registry of Hepatic Metastases has collected data on consecutive patients from 24 institutions who have undergone hepatic resection for colorectal carcinoma metastases. Patterns of recurrence were examined in a subgroup of 607 patients who had undergone curative resection of isolated hepatic metastases. Forty-three percent of these patient have had recurrences in the liver and 31% have had recurrences in the lung (either alone or in combination with other organs). A multivariate analysis showed that patients with positive pathologic margins or bilobar metastases were at an increased risk of having a recurrence in the liver (68% and 64%, respectively). We conclude that: hepatic resection effectively controls hepatic tumor in a substantial number of patients, adjuvant therapy after hepatic resection should be directed at both the lung and liver to significantly increase survival, and patients with positive pathologic margins or bilobar metastases are at an increased risk for hepatic recurrence.

The ileal stoma and protal hypertension: an uncommon site of variceal bleeding.

Patients who have chronic ulcerative colitis coexisting with liver disease and portal hypertension may suffer hemorrhagic parastomal varices after proctocolectomy and ileostomy. Large portal systemic collateral vessels between the superior mesenteric venous tributaries and the abdominal wall can be demonstrated by portal venography. Hemorrhage occurs from the mucocutaneous junction, a vulnerable point in this collateral circuit. Management by major and minor stomal revisions has been unsuccessful. Three patients who have bled from stomal and from esophagogastric varices were treated with portasystemic shunts. None of the three has had recurrent bleeding or postshunt encephalopathy during the 19 to 27 months after these operations.

Hepatic resection for intrahepatic ductal stones.

Intrahepatic stones that have caused irreversible ductal damage may need unusual treatment. When other treatments fail, resection of the affected portion of the liver is usually curative. Clinical features may be misleading: pain and sepsis are common, but jaundice is not. Diagnosis depends on awareness and critical use of special tests; ducts unseen may be culprits. Resection most often is easy, for usually the left hepatic ducts are affected.

Surgical treatment of hepatic metastases from colorectal cancers.

Follow-up data covering periods of two to 23 years have been collected on 60 patients who had resection of hepatic metastases for colorectal cancer. Multiple lesions were removed from 20 patients, and solitary lesions were excised from the other 40 patients. Only one patient died during hospital convalescence. No patient who had multiple lesions excised lived for five years. In contrast, 15 of the 36 patients eligible for five-year survival study who had resection of apparent solitary lesions lived for five years or more, and eight patients were alive without evidence of recurrence ten years or more after operation. These surprisingly favorable results of surgical treatment were analyzed in relation to results in patients who had biopsy specimens taken of lesions of comparable size and number, but no removal at the time of colonic resection. No patient in this control group lived for five years. Aggressive surgical treatment of apparent solitary hepatic metastatic lesions from colorectal cancer seems to be justified by the survival rate of surgically treated patients.

The distal splenorenal shunt.

Our initial use of the distal splenorenal shunt (DSRS) in 1973 was fostered by disappointment with the results of so-called total shunts. This selective shunt was, when anatomically feasible, our preferred therapy until 1980, when surgical referral was affected by enthusiasm for sclerotherapy. Our study of 71 DSRSs is uncontrolled because we could not recruit patients for a prospective randomized trial that involved either no treatment of operations that had proven faults. Our experience shows that operative risk (4%) and incidence of postshunt encephalopathy (6%) are low, that the rate of shunt occlusion is acceptable (10%), and that bleeding is as well controlled as with other shunts. Survival rates correlate with the cause of portal hypertension and with hepatic functional reserve. Analysis of the causes of death shows that the natural history of cirrhosis and coexistent disease are major determinants of prognosis.

Biliary decompression in hilar obstruction. Round ligament approach.

In some patients with biliary obstruction, access to the hepatic hilus is hindered by extensive tumor or by dense vascular scar tissue. In such patients, the biliary tract may be decompressed via the left hepatic duct away from the affected hilus. Access to the left hepatic duct in the left intersegmental plane is gained by dividing the round ligament, freeing it from the undersurface of the liver, and following it to its junction with the left portal vein. The left hepatic duct, which lies superior to the vein, is exposed by dividing the liver overlying the round ligament in the relatively avascular plane between the lateral and the medial segments of the left hepatic lobe. Decompression can be effected by simple tube drainage or, if the duct is large enough, by Roux-en-Y hepaticojejunostomy.

Stromal invasion of cancer in pedunculated adenomatous colorectal polyps: significance for surgical management.

Fifty-three patients were treated for pedunculated adenomatous polyps that contained foci of invasive cancer confined to the stroma. This entity is a stage of malignant involvement intermediate between in situ carcinoma and frank infiltrative cancer that invades the muscularis mucosae. Metastases to regional lymphatics were not observed. Local removal of such lesions without regional lymphadenectomy is adequate treatment.

Conventional splenorenal shunts. A reconsideration.

From 1961 to 1971, 73 central splenorenal and 66 portacaval shunts were done for cirrhotic patients who had bled from esophageal varices. Comparative analysis revealed low (3% and 2%, respectively) operative mortality for elective operations, equal (93%) effectiveness in control of variceal bleeding, but substantial diferences in the incidence of postshunt encephalopathy. For patients who had mimal hepatic dysfunction before operation, disabling disorders in mentation developed in 5% of patients who had splenorenal shunts, in contrast to 50% of patients who had portacaval shunts. Survival rates after the two shunts were nearly identical. Thus, the advantages of splenorenal shunts concern the quality of life but not the length of survival. These observations are considered in relation to available therapeutic alternatives.