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The surgical significance of carcinoma of the gallbladder
Carcinoma of the Gallbladder
The Surgical Significance
1.
BEAN PEMBERTON, MD; Chicago, Illinois WILLIS F. DIFFENBAUGH, MD, Chicago, Illinois E. LEE STROHL, MD, Chicago, Illinois
Since carcinoma of the gallbladder often presents bizarre and obscure clinical manifestations, the correct preoperative diagnosis is difficult to make. When it is limited to the gallbladder, carcinoma of the gallbladder, which is often associated with cholelithiasis, is curable by cholecystectomy [I]. Nevertheless, after this diagnosis is established, most patients die from this malignancy with great rapidity. The reasons for this rapid death remain to a large extent unexplained. We investigated our patients with carcinoma of the gallbladder to discover unusual features for earlier preoperative diagnosis, primary cause of death, responses to various treatments, and changes in survival rate. Methods We reviewed the courses of forty-one patients with carcinoma of the gallbladder from 1959 to 1969 at Presbyterian-St. Luke’s Hospital in Chicago, and added these cases to the fifty-nine that had previously been reported [21. Each chart of the recent patients was examined to obtain the following data: date of diagnosis, preoperative diagnosis, date of death, length of survival, presenting signs and symptoms, laboratory results, roentgenograms, surgical treatment, chemotherapy, radiotherapy, primary cause of death, and autopsy findings. These parameters in both recent and older cases are combined to make a total of 100 patients, which means that the percentage equals the number of patients with any particular feature. Furthermore, the two groups were compared to discover any changes that might have occurred in the past decade. Results
The correct preoperative diagnosis was made in only five patients. The patient’s symptoms simulated abdominal problems, such as hiatal hernia,
From the Division of Surgery, Center. Chicago, Illinois. l Present address: Department Columbus. Georgia.
Volume
122,
September
1971
Rush-Presbyterian-St of
Surgery.
The
Luke’s
Medical
Medical
Center,
duodenal ulcer, and appendicitis as well as other abdominal diseases of the right upper quadrant. There were sixty-five female and thirty-five male patients. Seventy-three patients were over sixty years of age with an average age of sixtyseven. The oldest patient was ninety-one whereas the youngest was thirty-two years old. Although there were some unusual presenting complaints, these patients had few characteristics that were diagnostic of carcinoma of the gallbladder. Jaundice from obstruction of the common bile duct occurred in thirty-five patients with only one survivor. The late signs of weight loss and fatigue occurred in fifty-one patients with no survivors. In contrast to its frequency in other malignant diseases, anemia occurred in only fifteen patients. Severe, constant epigastric pain, reported as characteristic of carcinoma of the gallbladder, was present in forty-four patients whereas twenty patients had little or no pain. Twenty per cent of our forty-one recent patients presented with ascites, indicative of intraperitoneal spread and peritoneal implants of carcinoma. In addition, in the recent group, 10 per cent presented with duodenal obstruction secondary to direct extension of the gallbladder carcinoma, whereas 78 per cent had gallstones associated with this tumor. Of the total group, ninety-two patients died after an average survival of four months. Forty-one died during the initial hospitalization. Sixty patients presented with far advanced disease. Fifteen of these had no surgical procedure whereas the other forty-five patients underwent exploration and biopsy. Surgical extirpation was used to treat forty patients. In the past decade, two patients underwent extensive resection which included portions of the liver, biliary tract, and duodenum, but both died in the early postoperative period. The remaining thirty-eight patients were treated with cholecystectomy alone.
381
Pembetton,
Diffenbaugh,
TABLE
Recent Survivors of Carcinoma of the Gallbladder Treated by Cholecystectomy
I
and,
Strohl
Length of Survival (yr)
Cholelithiasis
Tumor of the gallbladder Chronic cholecystitis and cholelithiasis Chronic cholecystitis and cholelithiasls Acute cholecystitis and
6.5 2 2
No Yes Yes
choledocholithiasis 5. Cholecystitis and cholelithlasis 6. Chronic cholecystitis and cholelithiasis
3.5 3 8.5
Yes Yes Yes
Preoperative 1. 2. 3. 4.
Diagnosis
Eight patients who underwent cholecystectomy have survived for more than two years. The length of survival along with the preoperative diagnoses of the six recent survivors is given in Table I. The recent group of patients have an over-all survival rate of 14.6 per cent. In our total group of survivors, two patients had no gallstones. Surprisingly, one patient, who had a resected specimen that showed gallbladder carcinoma in a lymph node, has lived four years with no evidence of residual disease. Four patients treated with 5-fluorouracil in the past decade have had no observable response. The usual cause of death was respiratory failure followed by cardiac arrest. Of the thirty-five patients dying in the past decade, twenty-one had ex-
Lymphatic drainage of the gallbladder area. Figure 1. (From: Rouiere H: Anatomy of the Human Lymphatics. Translated by Tobias MJ. Ann Arbor, Michigan, Edwards Bras, Inc, 1938. Figure 98, p 199.)
382
tensive pneumonitis, with half of these patients exhibiting severe dehydration. Five patients died of pulmonary emboli. Of the other nine patients, the cause of death was gastrointestinal hemorrhage in two patients, unknown in four patients, and myocardial infarction, stroke, and lung metastases in each of the three remaining patients. No patient died from liver failure. Comments
Carcinoma of the gallbladder spreads in a characteristic and unique way. This neoplasm usually metastasizes either by direct extension or through the lymphatics. Arising from the gallbladder mucosa, this carcinoma extends through the gallbladder wall to involve contiguous parts of the liver, common bile duct, or duodenum. If the tumor penetrates the serosa of the gallbladder, cells may spread to the abdominal cavity and produce peritoneal implants. This intra-abdominal extension of gallbladder carcinoma causes ascites, which signified incurable disease in our patients. Liver metastases occur both by direct penetration through the gallbladder bed and through the lymphatics of Glisson’s capsule. The lymphatic drainage of the gallbladder is illustrated in Figure 1. Multiple gallbladder lymphatics drain into nodes around the cystic and common bile ducts. From this first echelon, carcinoma of the gallbladder spreads to peripancreatic and aortic lymph nodes [a]. Although the pancreatic surface in our patients was involved with extrinsic tumor and metastatic nodes, the pancreas itself was not replaced by this neoplasm. While metastases proceed from abdominal lymphatics to mediastinal lymph nodes and the blood stream, the first site of distant metastasis outside the abdomen is the lung. Although pulmonary metastases are the most common, carcinoma of the gallbladder has spread to almost every organ of the body. Although ninety patients had carcinoma of the gallbladder confined to the abdomen, the average survival of our patients was only four months. Since the rapidity of the patient’s death often failed to correspond to the extent of disease, we wondered what caused these patients to die. Involvement of the respiratory system was the primary cause of death in 90 per cent of our recent cases. Bronchopneumonia develops in patients with carcinoma of the gallbladder which eventually causes respiratory arrest. Since these patients have profound anorexia and fatigue, they become dehydrated and malnourished. Dehydration contributes to developing bronchopneumonia and
The American
Journal
of Surgery
Carcinoma
rapid deterioration of the patient’s condition. Another abnormality that produces respiratory death is pulmonary embolus. Fatigue, immobility, and dehydration in these patients produce stasis, thrombosis, and subsequent emboli. Interestingly, carcinoma of the gallbladder usually causes death by producing malnutrition, immobility, and dehydration, but not by replacement or failure of a vital organ from the neoplasm itself. The survival rate of patients with carcinoma of the gallbladder has changed from 3.4 per cent in our former patients to 14.6 per cent in our recent patients. This increased salvage of patients in the past decade suggests that this disease is curable. One patient who survived with metastatic carcinoma in a lymph node demonstrates that limited lymph node involvement is compatible with complete surgical extirpation. Since no patient benefited from either radical surgery or chemotherapy, increased survival in these recent patients may reflect a more common use of surgery for diseased gallbladders. Early diagnosis of carcinoma of the gallbladder remains a difficult problem [4,5]. Although severe, constant epigastric pain is described as characteristic of this lesion, less than half of our patients had this symptom. No other finding in these patients provides a clue to early detection of this malignant lesion, except for the presence of cholelithiasis. Since cholecystectomy was the only form of treatment in all of our eight survivors, this operation is apparently curative treatment for carcinoma of the gallbladder at an early stage. From a theoretic point of view, limited wedge resection of the liver adjacent to the gallbladder bed and excision of biliary lymph nodes [6] by skeletonizing
Volume 122. September 1971
of Gallbladder
the gastrohepatic ligament with preservation of the common bile duct, hepatic artery, pancreas, and duodenum may have some merit in patients with localized disease. In our opinion, extensive radical surgery has little place in the treatment of carcinoma of the gallbladder. Summary
The courses of forty-one patients with carcinoma of the gallbladder from 1959 to 1969 were reviewed, and these cases were added to the fiftynine that had previously been reported. Eight of these 100 patients survived more than two years, six within the last decade. Only five patients had a correct preoperative diagnosis. Respiratory failure was the usual cause of death in our recent group of patients. Early cholecystectomy for cholelithiasis may account for increased salvage in recent patients. Although radical surgical extirpation is not recommended, limited wedge resection of the liver and excision of biliary lymph nodes may have some merit. References 1. Strauch GO: Primary carcinoma 2. 3.
4. 5.
6.
of the gallbladder. Surgery 47: 368, 1960. Strohl EL, Diffenbaugh WG: Carcinpma of the gallbladder. Arch Surg 70: 772, 1955. Fabim RB, McDonald FR. Riahards JG, Ferris DO: Carcinoma of the gallbladder. A study of its modes of soread. Ann Sure 156: 171. 1962. Lirwin’ MS: Prima< carcinoma of the gallbladder. Arch Surg 95: 236, 1967. Robertson WA, Carlisle BB: Primary carcinoma of the gallbladder. Review of 52 cases. Amer J Surg 113: 738, 1967. Wolma FJ. Lynch JB: Primary carcinoma of the gallbladder. The importance of lymph node dissection in early cases. Arch Surg 83: 657, 1961.
383
The Surgical Significance
1.
BEAN PEMBERTON, MD; Chicago, Illinois WILLIS F. DIFFENBAUGH, MD, Chicago, Illinois E. LEE STROHL, MD, Chicago, Illinois
Since carcinoma of the gallbladder often presents bizarre and obscure clinical manifestations, the correct preoperative diagnosis is difficult to make. When it is limited to the gallbladder, carcinoma of the gallbladder, which is often associated with cholelithiasis, is curable by cholecystectomy [I]. Nevertheless, after this diagnosis is established, most patients die from this malignancy with great rapidity. The reasons for this rapid death remain to a large extent unexplained. We investigated our patients with carcinoma of the gallbladder to discover unusual features for earlier preoperative diagnosis, primary cause of death, responses to various treatments, and changes in survival rate. Methods We reviewed the courses of forty-one patients with carcinoma of the gallbladder from 1959 to 1969 at Presbyterian-St. Luke’s Hospital in Chicago, and added these cases to the fifty-nine that had previously been reported [21. Each chart of the recent patients was examined to obtain the following data: date of diagnosis, preoperative diagnosis, date of death, length of survival, presenting signs and symptoms, laboratory results, roentgenograms, surgical treatment, chemotherapy, radiotherapy, primary cause of death, and autopsy findings. These parameters in both recent and older cases are combined to make a total of 100 patients, which means that the percentage equals the number of patients with any particular feature. Furthermore, the two groups were compared to discover any changes that might have occurred in the past decade. Results
The correct preoperative diagnosis was made in only five patients. The patient’s symptoms simulated abdominal problems, such as hiatal hernia,
From the Division of Surgery, Center. Chicago, Illinois. l Present address: Department Columbus. Georgia.
Volume
122,
September
1971
Rush-Presbyterian-St of
Surgery.
The
Luke’s
Medical
Medical
Center,
duodenal ulcer, and appendicitis as well as other abdominal diseases of the right upper quadrant. There were sixty-five female and thirty-five male patients. Seventy-three patients were over sixty years of age with an average age of sixtyseven. The oldest patient was ninety-one whereas the youngest was thirty-two years old. Although there were some unusual presenting complaints, these patients had few characteristics that were diagnostic of carcinoma of the gallbladder. Jaundice from obstruction of the common bile duct occurred in thirty-five patients with only one survivor. The late signs of weight loss and fatigue occurred in fifty-one patients with no survivors. In contrast to its frequency in other malignant diseases, anemia occurred in only fifteen patients. Severe, constant epigastric pain, reported as characteristic of carcinoma of the gallbladder, was present in forty-four patients whereas twenty patients had little or no pain. Twenty per cent of our forty-one recent patients presented with ascites, indicative of intraperitoneal spread and peritoneal implants of carcinoma. In addition, in the recent group, 10 per cent presented with duodenal obstruction secondary to direct extension of the gallbladder carcinoma, whereas 78 per cent had gallstones associated with this tumor. Of the total group, ninety-two patients died after an average survival of four months. Forty-one died during the initial hospitalization. Sixty patients presented with far advanced disease. Fifteen of these had no surgical procedure whereas the other forty-five patients underwent exploration and biopsy. Surgical extirpation was used to treat forty patients. In the past decade, two patients underwent extensive resection which included portions of the liver, biliary tract, and duodenum, but both died in the early postoperative period. The remaining thirty-eight patients were treated with cholecystectomy alone.
381
Pembetton,
Diffenbaugh,
TABLE
Recent Survivors of Carcinoma of the Gallbladder Treated by Cholecystectomy
I
and,
Strohl
Length of Survival (yr)
Cholelithiasis
Tumor of the gallbladder Chronic cholecystitis and cholelithiasis Chronic cholecystitis and cholelithiasls Acute cholecystitis and
6.5 2 2
No Yes Yes
choledocholithiasis 5. Cholecystitis and cholelithlasis 6. Chronic cholecystitis and cholelithiasis
3.5 3 8.5
Yes Yes Yes
Preoperative 1. 2. 3. 4.
Diagnosis
Eight patients who underwent cholecystectomy have survived for more than two years. The length of survival along with the preoperative diagnoses of the six recent survivors is given in Table I. The recent group of patients have an over-all survival rate of 14.6 per cent. In our total group of survivors, two patients had no gallstones. Surprisingly, one patient, who had a resected specimen that showed gallbladder carcinoma in a lymph node, has lived four years with no evidence of residual disease. Four patients treated with 5-fluorouracil in the past decade have had no observable response. The usual cause of death was respiratory failure followed by cardiac arrest. Of the thirty-five patients dying in the past decade, twenty-one had ex-
Lymphatic drainage of the gallbladder area. Figure 1. (From: Rouiere H: Anatomy of the Human Lymphatics. Translated by Tobias MJ. Ann Arbor, Michigan, Edwards Bras, Inc, 1938. Figure 98, p 199.)
382
tensive pneumonitis, with half of these patients exhibiting severe dehydration. Five patients died of pulmonary emboli. Of the other nine patients, the cause of death was gastrointestinal hemorrhage in two patients, unknown in four patients, and myocardial infarction, stroke, and lung metastases in each of the three remaining patients. No patient died from liver failure. Comments
Carcinoma of the gallbladder spreads in a characteristic and unique way. This neoplasm usually metastasizes either by direct extension or through the lymphatics. Arising from the gallbladder mucosa, this carcinoma extends through the gallbladder wall to involve contiguous parts of the liver, common bile duct, or duodenum. If the tumor penetrates the serosa of the gallbladder, cells may spread to the abdominal cavity and produce peritoneal implants. This intra-abdominal extension of gallbladder carcinoma causes ascites, which signified incurable disease in our patients. Liver metastases occur both by direct penetration through the gallbladder bed and through the lymphatics of Glisson’s capsule. The lymphatic drainage of the gallbladder is illustrated in Figure 1. Multiple gallbladder lymphatics drain into nodes around the cystic and common bile ducts. From this first echelon, carcinoma of the gallbladder spreads to peripancreatic and aortic lymph nodes [a]. Although the pancreatic surface in our patients was involved with extrinsic tumor and metastatic nodes, the pancreas itself was not replaced by this neoplasm. While metastases proceed from abdominal lymphatics to mediastinal lymph nodes and the blood stream, the first site of distant metastasis outside the abdomen is the lung. Although pulmonary metastases are the most common, carcinoma of the gallbladder has spread to almost every organ of the body. Although ninety patients had carcinoma of the gallbladder confined to the abdomen, the average survival of our patients was only four months. Since the rapidity of the patient’s death often failed to correspond to the extent of disease, we wondered what caused these patients to die. Involvement of the respiratory system was the primary cause of death in 90 per cent of our recent cases. Bronchopneumonia develops in patients with carcinoma of the gallbladder which eventually causes respiratory arrest. Since these patients have profound anorexia and fatigue, they become dehydrated and malnourished. Dehydration contributes to developing bronchopneumonia and
The American
Journal
of Surgery
Carcinoma
rapid deterioration of the patient’s condition. Another abnormality that produces respiratory death is pulmonary embolus. Fatigue, immobility, and dehydration in these patients produce stasis, thrombosis, and subsequent emboli. Interestingly, carcinoma of the gallbladder usually causes death by producing malnutrition, immobility, and dehydration, but not by replacement or failure of a vital organ from the neoplasm itself. The survival rate of patients with carcinoma of the gallbladder has changed from 3.4 per cent in our former patients to 14.6 per cent in our recent patients. This increased salvage of patients in the past decade suggests that this disease is curable. One patient who survived with metastatic carcinoma in a lymph node demonstrates that limited lymph node involvement is compatible with complete surgical extirpation. Since no patient benefited from either radical surgery or chemotherapy, increased survival in these recent patients may reflect a more common use of surgery for diseased gallbladders. Early diagnosis of carcinoma of the gallbladder remains a difficult problem [4,5]. Although severe, constant epigastric pain is described as characteristic of this lesion, less than half of our patients had this symptom. No other finding in these patients provides a clue to early detection of this malignant lesion, except for the presence of cholelithiasis. Since cholecystectomy was the only form of treatment in all of our eight survivors, this operation is apparently curative treatment for carcinoma of the gallbladder at an early stage. From a theoretic point of view, limited wedge resection of the liver adjacent to the gallbladder bed and excision of biliary lymph nodes [6] by skeletonizing
Volume 122. September 1971
of Gallbladder
the gastrohepatic ligament with preservation of the common bile duct, hepatic artery, pancreas, and duodenum may have some merit in patients with localized disease. In our opinion, extensive radical surgery has little place in the treatment of carcinoma of the gallbladder. Summary
The courses of forty-one patients with carcinoma of the gallbladder from 1959 to 1969 were reviewed, and these cases were added to the fiftynine that had previously been reported. Eight of these 100 patients survived more than two years, six within the last decade. Only five patients had a correct preoperative diagnosis. Respiratory failure was the usual cause of death in our recent group of patients. Early cholecystectomy for cholelithiasis may account for increased salvage in recent patients. Although radical surgical extirpation is not recommended, limited wedge resection of the liver and excision of biliary lymph nodes may have some merit. References 1. Strauch GO: Primary carcinoma 2. 3.
4. 5.
6.
of the gallbladder. Surgery 47: 368, 1960. Strohl EL, Diffenbaugh WG: Carcinpma of the gallbladder. Arch Surg 70: 772, 1955. Fabim RB, McDonald FR. Riahards JG, Ferris DO: Carcinoma of the gallbladder. A study of its modes of soread. Ann Sure 156: 171. 1962. Lirwin’ MS: Prima< carcinoma of the gallbladder. Arch Surg 95: 236, 1967. Robertson WA, Carlisle BB: Primary carcinoma of the gallbladder. Review of 52 cases. Amer J Surg 113: 738, 1967. Wolma FJ. Lynch JB: Primary carcinoma of the gallbladder. The importance of lymph node dissection in early cases. Arch Surg 83: 657, 1961.
383