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Management of bowel obstruction in advanced cancer patients
Vol. 9 No. 3 April I994
Journal of Pain and Symptom Management
I93
Pain Therapr and Pczlliative Care Division, National Cancer Institute, Milan, Ita&
Bowel obstruction is a common and distressing outcom in patients with abdominal or pelvic cancer. JR&2 surgery must remain the primary treatmentfor malignant obstruction, it is now recognized that there is a group of patch with advan~d d&ease or poor general ~~~t~o~ who are unfit fm surgq and require alternative m.anagem& to relieve distressing symptoms. A number of treatmnt optiorw are now available j&r the patient with advanced cancer who akte@s intestinal obstmction. This reuitzwexamines the indications fm surgery, the use of n~og~t~ tube and ~~~~~~0~ g~trostomy, and t~p~a~e of drugsfor symp~m co~t~o~~ J Pain Symptom Manage ~994;9:~93-2~~.
Bowel obstruction, advanced and terminal cancer patients
Bowel obstruction
is a common and distressing outcome in the course of malignancies primary within or metastatic to the peritoneal cavity. This complication may arise at any time, but is more likely during the advanced stages of disease. The incidence ranges from 5.5% to 42% in ovarian carcinoma and from 10% to 28.4% in colorectal cancer (Table 1). Table 2 shows the time from diagnosis of cancer to surgery for intestinal obstruction. According to
Address reprint requests to: Carla Ripamonti,
MD,
Pain ‘Iherapy and Palliative Care Division, National
Cancer Institute, via Venezian 1,20133 Milan, Italy. Acceptedfwpublication: September 22, 1993. A version of this paper was originally presented in June 1993 at the meeting “Cancer Care for the 1990s-Supportive Care Issues,” jointly sponsored by Calvary Hospital, Higushi Sapporo Hospital, and Memorial Sloan-Kettering Cancer Center. 0 U.S. Cancer Pain ReiiefCommittee,1994 Published by Elsevier, New York, New York
Gallick and colleagues, the time interval ap pears to be signitlcandy longer for i~~abdominal (mean, 22.4 mo) than extraabdominal (mean, 57.5 mo) tum0rs.r
The most frequent tion are as follows: 1 ~~~~~
causes of bowel obstrun-
occ~~~o~ of the Eunzen. This may be due to enlargement of the primary tumor or omental and mesenteric recurrence, masses, abdominal or pelvic adhesions, or postir~diation fibrosis2 Pancreatic cancer tends to spread directly to the duodenum or stomach, while cancer of the colon spreads to the jejunum and ileum. Prostate and bladder cancer spread to the rectumS5 Tumors at the splenic flexure can cause an obstruction in 49% of cases, while tumors of right and left colon obstruct in 25% of cases.
Incidence
Table I of Bowel Obstruction in Cancer Patients
Authors
Primary cancer
Castaldo et al.24
ov=ly @ary
Tunca et al.” Solomon et al.4O Baines et al.’
R 5.5 25 14.7
Baines et al.’
ovary Colorectal Miscellaneous
Phillips et al.’
Large bowel
16
Kyllonen4r
Colon Rectum
24 4.4
Kyllonen4’ So0 et al.t3
Gynecologic
10” 3”
5
Lund et al.”
0vat-y
14
Beattie et aL4* SteinerY7
ovaly Various
42” 6
QAdvanced cancer.
Only 6% of tumors rectosigmoid junction tion.4 9_.
Vol. 9 No. 3 April I994
Ripamonti
194
of the rectum and cause bowel obstruc-
Intraluminal occlusion of the lumen. This may be due to polypoid lesions due to primary cancer or metastases or annular tumor-al dissemination.
3. Intramural occlusion qf the lumen. This may, for example, be due to infiltration of intestinal muscles (intestinal linitis plastica). 4. Intestinal motility disorders ($wu&obstruction). This may be due to infiltration of the mesentery or bowel muscle and nerves, malignant involvement of the celiac plexus,” or pamneoplastic neuropathy in patients with lung cancer. s Pseudoobstruction is a condition that presents the signs and symptoms of bowel obstruction without a mechanical block. Bowel obstruction is often due to multifactorial causes. In addition to those listed above, the presence of inflammatory edema, fecal impaction, and the administration of constipating drugs may also contribute to the development of intestinal obstruction.
In advanced cancer obstruction is rarely an gradually worsen until ous, and their presence
patients, the onset of acute event. Symptoms they become continuand intensity depends
on the level involved. The symptoms, which are
almost always present, are intestinal colic (reported by 72%-76% of patients); abdominal pain due to distension, hepatomegaly, or tumor masses (I: *i.:orted by 92%) ; and vomiting (68%-100%).7~* Vomiting can be intermittent or continuous; it develops early and in large amounts in gastric, duodenum, and small bowel obstruction, and develops later in large bowel obstruction. Abdominal distension, visible peristalsis, intermittent borborygmi, and anorexia are commonly manifested in patients with bowel obstruction. In cases of complete obstruction, constipation is present for feces and fla.tus. Sometimes overflow diarrhea results from bacterial liquefaction of the fecal material blocked in the sigmoid colon or rectum. Abdominal radiographs taken in supine or standing position are the first investigations to be performed in patients with suspected bowel obstruction. This is done to document the dilated loops of the intestines, or air-fluid interfaces, or both. The study of the small bowel with contrast can distinguish an obstruction due to metastases, radiation bowel damage, or adhesions.”
Treatment w8F-?Y In advanced cancer patients, guidelines for conservative versus surgical treatment are still conflicting. The decision is further complicated by the fact that the causes of the obstruction may be benign (from 6.1% in ovarian cancer to 48% in colorectal cancer) (Table 3).l”
T&L 2 Time from Cancer Diagnosis to Obstruction Authors
Primary cancer
Stage
Tunca et al.**
Ovary
All
Rubin et al.18 Beattie et al.42
CvarY Ovary
All All
29.0 mean
Advanced
19.0 median 15.0 median
Advanced
18.0 median
Spears et al.rO Colorectal Turnbull et al.r4 Carcino matosis Aabo et al.21 Abdominalpelvic
Months 8.3 median 13.1 mean
Vd. 9 No. 3 Apil I994
Management of Bowel Obstruction
Table 3 Rate of Bowel Obstruction due to Benign Causes in Advanced Cancer Patients patients
Primary cancer
NO.
Authors
Benign causes(%) e.--
So0 et al.‘”
64
Gynecologic
Clarke-Pearson et al.43
49
Omly
Tunca et al.11
127
Gallick et al.’
50
Various
26.0
OMty
34.0 6.1 9.4
Osteen et a1.44
66
variuus
31.8
Spears et al. IU
62
Colorectal
48.0
Aabo et al>!
41
Various
12.0
Annest and Jolly”
34
Various
3.0
Not all patients are suitable candidates for surgery. The rate of inoperable patients ranges from 6% to 50% according to different authors.ll-lg The most frequent causes reported in the literature are (a) extensive tumor, (b) multiple partial obstructions, and (c) surgical correction impossible. Benefit from surgery is defined as at least 60 days of survival after operation.2u This defmition, however, does not take into account the well-being of the patient, the presence or absence of symptoms, postoperative complications, or the length of hospitalization. In the study by Lund and colleagues,t* for example, 56% of patients survived 60 days after operation, but 43% of this group manifested intermittent symptoms of incomplete and complete intestinal obstruction until death. Thus, surgery does not always solve the problem of obstruction or eliminate symptoms in advanced cancer patients. In a large percentage of cases, it can lead to further complications (such as wound infections and/or dehiscence, sepsis, enterocutaneous fistula, further obstruction, peritoneal abscess, anastomosis dehiscence, gastrointestinal bleeding, pulmonary embolus, or deep venous thrombosis). Table 4 shows the rates of operative mortality (defined as death from any cause within 30 days of the operation) and morbidity, and the length of survival after surgery for bowel obstruction in cancer patients. Several authors have pointed out the need for prognostic criteria to help doctors in selecting patients who are likely to benefit from surgical intervention. Poor prognostic factors
I95
include (1) intestinal motility problems due to diffuse intraperitoneal carcinomatosis;“,lF’~~” (2) cache&c patients over 65 yr;ls (3) ascites requiring frequeut paracentesis;tzs (4) 10~ serum albumin level;2s (5) previous radiotherapy of the abdomen or pelvis;16.24 (6) palpable intraabdominal masses and liver involvement, or distant metastases, pleural effusion, or pulmonary metastases; 1.t1,ts,22(7) multiple partial bowel obstructions with prolonged passage time on radiograph examination;tt and (8) poor performance statusI
Nasogastric Suction and Intravenous Fluids The usual hospital treatment for symptom control is nasogastric suction and liquid supplementation (“drip and suck”). This is useful in decompressing the stomach and/or intestine, and for correcting fluid and electrolyte imbalance before surgery is performed or while a treatment decision is under consideration. The tube often becomes occluded and requires flushing and/or replacement. During longterm drainage, the nasogastric tube can interfere with cough for clearing pulmonary secretions and may be associated with nasal cartilage erosion, otitis media, aspiration pneumonia, and esophagitis with erosion and bleeding.*” Prolonged nasogastric suction and intravenous fluids for symptomatic treatment of inoperable patients is not recommended. This treatment can create discomfort in patients who are already distressed by previous anticancer and surgical therapies. Such methods are regarded by patients as barriers between them and family members, as they often require hospitalization. An alternative therapy for symptom management has to be found for these patients.
Percutaneous Gastrostomy Percutaneous gastrostomy (PG) introduces a tube into the stomach through the abdominal wall without requiring surgical intervention or regeneral anesthesia. *6S’ This technique quires a brief hospitalization (an average of 4.6 days in one survey). For this reason, PG can be performed safely in advanced cancer patients as a venting procedure for the treatment of nausea and vomiting due to bowel obstruction. to be superior to both It. is widely consideae nasogastric suction and operative gastrostomy for palliation of small bowel obstruction.
Vol. 9 No. 3 ApriE 1994
Ripmmti
196
No. Patients
Authors
Primary cancer
JO-Day mortality (%)
Other operative complications (%I
Survival (mo)
So0 et al.‘s
64
Gynecoiogic
11
15.5
2.5 median
Lund et al.”
25
@Qry
32
32
2.0 median
Rubin et al.tR
43
ovary
9
Castaldo et a1.a4 ClarkePearson et a1.4s
23 49
@ary ovary
13 14
Rrebs and Gopierud’”
93
ovary
Tunca et ai.”
90
Ovary
Piver et al.‘”
60
Ovary
16.5
Beattie et aL4a Walsh and Schofield”
11 36
ovary Various
Aranha et al.“s Aranha et aL4s Osteen et a1.44 Aabo et aLat Chan and Woodru@s Annest and Jollyi Turnbull et ai.t4
40 26 32 41 10 34 89
Various Various Various Various various Various Abdominal
-,
Nor
11.5
6.8 median
43 49
17% lyr 4.5 median
12
12
3.1 median
14
-
7.0 mean
31
2.5 median
9 19
9
7.0 mean 11 median
27.5 46 24.4 40 18 13
22.5 15.0 30 44 44
7.0 4.5 3 4.5 2 4.0 4.5
mean mean median median median mean mean
rcyortcd.
Gemlo and colleague@ reported the experience of 27 inoperable terminally ill patients with abdominal cancer and partial or complete bowel obstruction, A central venous catheter was placed in all patients for administration of 2-3 L of standard electrolyte solution and drugs (opioids, antiemetics, and antispasmotics) when oral and rectal routes of adminis~tion were not viable. In 13 patients, a venting gastrostomy connected to passive drainage was performed to control intractable vomiting due to complete obstruction. All patients were cared for at home by nurses after an average stay in the hospital of 11.2 days. During this period, the patients and their families underwent extensive training in the use of these catheters, infusion pumps, and gastrostomy tubes. There were no complications with gastrostomies. Vomiting was controlled and, with the a~ilabili~ of in~ve~ous (IV) infusion, few patients complained of hunger and none complained of thirst. The average length of survival in these patients was 64 days (range, Q-223 days). P~~~~C#lO~,~
T~~~~t
The few published studies in which symptom control is successfully achieved by administra-
tion of analgesic, anticholinergic, and antiemetic drugs (Tables 5 and 6), without the use of decompressive tube or IV fluids-come from hospices’ or palliative care units.“~*‘~s* Baines and colleagues’ were the first to report the successful control of nausea, vomiting, and pain by means of a pharmacologic approach in 38 patients with bowel obs~~tion due to advanced cancer. Drugs were administered either by mouth, continuous subcutaneous (SC) infusion, or the rectal route. In 68% of the patients, intestinal colic was completely controlled using smooth muscle relaxants, such as scopolamine, atropine, and loperamide. Continuous abdominal pain due to distension, tumor mass, or hepatomegaly was relieved in 89% of the patients using various opioids, namely diamorphine, morphine, and oxycodone. Nausea and vomiting were the most difftcult symptoms to manage, and only 13% of the patients had no vomiting during treatment. Prochlorperazine, chlorpromazine, and haloperidol were effective antiemetics. Metoclopramide was not found to be effective and in fact worsened colicky pain. Thirteen patients somplained of diarrhea and were treated with antidiarrheal drugs, such as loper-
Vol. 9 WQ.3 April 1994
Management of Bowel Obstruction
Table 5
Nausea and Vomiting: Pharmacologic ThemPy 1. Hyoscine bu~lbrom~de 40-120 mg/day subcutane~usly.~~~ lt is possible to increase the dosage until xerostomia and drowsiness are tolerable for the patient. 2. Haloperidol5-15 mg/day subcutaneously.* It can be associated with hyoscine bu~lhromide in the same syringe. 3. Metoclopramide 60-240 mg/day subcutaneously.~Jt It was not used in B&es’s study7 as it may increase colic. In patients with incomplete bowel obstruction, metociop~ide at a dose of 10 mg subcu~neously every 4 hr was the drug of choice.3t 4. IIyoscine hydrobromide 0.3-2 mg/day subcntaneons1y.s 5. Cyciizine 100-150 mg/day subcutaneously or 50 mg every 8 hr rectally, It can be added to prochlorperazine suppositories and to haloperidol subcutaneously. Crystallization may occur at higher dosages or in association with other drugs.3 6. Me~o~imepra~ne 50-150 mg/day subcutane0usly.s It is very effective but it causes sedation and subcutaneous irritation. 7. Prochlorperazine 25 mg every 8 hr rectally. 8. Chlorpromazine 50-100 mg every 8 hr rectally or subcu~eously.3,s7 9. Dimenhydrinate 50-100 mg subcutaneously as needed.2s 10. Dexamethasone 20-40 mg/day,sSs7 3-60 mg/day.B 11. Octreotide 0.2-0.9 mg/day subcutaneousIy.YY~“LI.4~
amide and codeine. The average survival rate of these inoperable patients was 3.7 months after the onset of obstruction. Seven patients (18%) lived more than 7 montiis. This survival rate was longer than that reported by other authors using a similar approach.~,~,3* Ventafridda and colleague@ assessed another pharmacologic approach for the treatment of vomiting and pain in terminal cancer patients with inoperable g~~ointestin~ obstruction. Twenty-two symptomatic patients, who were judged to be inoperable, were treated with the combination of morphine hydrochloride and scopolamine butylbromide as analgesics and h~o~ridoi as an antiemetic. The drugs were administered by continuous SC infusion via a syringe driver or by IV infusion if a central venous catheter had been inserted previously. The period of treatment lasted 2-50 days (mean, 13.4 days; SD = 12.1). Seventeen
197
patients were treated at home and five in the hospital. In both cases, treatment continued until death. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (TO), 2 days after (T2), and 2 days before death {T-2). They showed that there was a significant decrease in the pain score (P c 0.001) on T2 and a further decrease on T-2 (P < 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastrir tube placement. Dry mouth showed an upward trend throughout the observation period (P c 0.05) but was successfully treated by administe~ng liquids by mouth or ice cubes to suck. Drowsiness also presented an upward trend from TO to T-2 (P < 0.001). Only one patient of the 16 who reported thirst required TVhyd~don. These data indicate that vomiting and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administ~tion of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasirgastric tube placement or lV hydration. Fainsinger and colfeaguesss reviewed the charts of 100 consecutive patients dying on the palliative care unit and identified 15 who required medical management of bowel obstruction. Three patients had a nasogastric tube placement for a short period of time
Table 6 Colic@
Pain: Pharmacologic Therapy
1. Hyoscine bu~lbro~de starting with 40-60 mg/ day up to 380 mg/day?ss 2. Hyoscine hydrobromide 0.3-2.0 mg/day subcutaneous1y.s 3. Hyoscine hy~obromide as needed.3
0.S0.6 mg sub~mgu~ly
4. Loperamide 2 mg four times daily.3 5.
Morphine subcutaatotisiy starting with 2.5 mg/hr increasing the dose until relief is achieved.s’
6. Transdermal scopolamine 1.5-3 mg every 3 days.“? 7. Celiac plexus block with alcohol. With all &erapies, gasuokirteticamiemeticslike tuett~ clopramideand doln~ddoxle aud stiIxiulantlax&ves should be discontinued.
198
Ripamonti
during admission to the hospital. A percutaneous gastrostomy was placed in four patients. Medications administered for nausea and vomiting included metoclopramide, dimenhydrinate, haloperidol, hyoscine butylbromide, domperidone, and cisapride. All 15 patient-5 received dexamethasone, and all received hp dradon by hypodermoclysis. The median opioid dose was equivalent to morphine 64 mg/day (range, 21-l&400 mg/day). Medical management for bowel obstruction was required for a mean of 18 days (median, 1’7days; range, 2-41 days). Isbister and colleagues”’ managed 24 patients with advanced abdominal cancer and previous operative or radiologic evidence of intestinal obstruction without surgery. Morphine was administered to control background pain and intestinal colic (mean dose, 9.2 mg/hr) and metoclopramide was used to control vomiting (mean dose, 6.9 mg/hr). A combination of drugs was administered through continuous SC infusion via a syringe driver. The average survival rate after the onset of complete obstruction was 29.2 days. No patient needed a nasogastric tube to control symptoms. De Conno and colleagues”” described the antiemetic role of scopolamine butylbromide administered SC by means of a syringe driver in three women with bowel obstruction due to advanced ovarian cancer. All patients were judged inoperable because of multiple sites of obstruction and were treated with nasogastric drainage and total parenteral nutrition through a central venous catheter. During daily administration of 120 mg, 120 mg, and 80 mg of scopolamine butylbromide, respectively, the quantities of gastrointestinal fluid drained through the nasogastric tube were significantly reduced. Moreover, during the first week of treatment, patients reported that the scopolamine butylbromide provided good relief of colicky pain. Later, morphine hydrochloride was added to the other drugs to control continuous abdominal pain. The nasogastric tube could be removed from all patients following the first week of anticholinergic therapy, which continued until death after 55 days, 172 days, and 54 days, respectively. Dry mouth was reported to be the most important side effect of this treatment, but patients tolerated it by sucking ice cubes and drinking small sips of water.
Vol. 9 No. 3 April 1994
In patients with symptoms due to bowel obstruction, the route of drug administration must be individualized. The oral route is not always possible. Although rectal and sublingual routes are very safe and useful in a home setting,J:! only a few drugs are available for these routes of administration. Those patients with previously inserted central venous catheters have IV access. Other patients can use continuous SC infusion by means of a portable syringe driver, which allows for the parenteral administmtion of different combinations of drugs with minimal discomfort for the patient and ease of use in a home setting. To control continuous abdominal pain, opioids like morphine, hydromorphone, or diamorphine have to be administered SC by a portable pump. Equianalgesic doses must be used when switching from the oral to parenteral route. Doses should be gradually increased until the symptom is controlled. Recently, octreotide, an analogue of somatostatin, has been evaluated as a therapy to control gastrointestinal secretions and vomiting in patients with bowel obstruction.“s*“4 This drug has a powerful inhibitory action on the secretion of gastrin, gastric acid, pancreatic juice, bile flow, and intestinal secretions, and also inhibits gastrointestinal motility and reduces venous splanchnic flow. Several authors have recommended the use of corticosteroids in bowel obstruction because they can reduce peritumoral inflammatory edema and thus improve intestinal passage. No controlled clinical trials have been performed and neither routes of administration nor dosing of these drugs has been standardized. MacDonald”” suggests treatment with either dexamethasone (beginning with 8 mg/day) or prednisone (beginnning with 25 mg every 12 hr); this author recommends gradual dose reduction when the response is positive. Reids” also reported using dexamethasone in initial doses of 20 mg/day for the temporary relief of gastrointestinal obstruction and/or nausea. If no response to dexamethasone occurs with increased doses (5-10 mg/day, SC), Steiner”’ advocates a single IV dose of 25 mg, followed by 100 mg if needed. According to Fainsinger and colleagues, *!) dexamethasone is a very useful agent in managing nausea and vomiting, but its role in preventing progression to complete bowel obstruction is impossible to determine.
Vol. 9 No. 3 April 1994
They administered dexamethasone range of 8 to 60 mg/day.rJ
Management of Bowel Obstmction
with
a
a?& Fainsinger and colleagues% suggest that the two main indications for maintaining hydration in terminal cancer patients are (a) the prevention of dehydration that may cause agitated confusion and (b) prevention of prerenal failure and the resulting accumulation of drug metabolites, such as morphine-Gglucuronide, that may result in complications such as myoclonus or seizure. When relief of obstructive symptoms is obtained through palliative treatment, patients are usually able to drink water and other fluids and to eat small amounts of their favorite foods.7*8*Y’*ss The role of total parenteral nutrition in the management of these patients is controversial.‘G~‘ONo data are available on the survival rates or quality of life in advanced cancer patients treated with this modality. We do not administer total parenteral nutrition in our clinical practice, but, rather, provide fluid by IV infusion (if a central venous catheter was previously used) or by hypodermoclysis2g*sg for control of symptoms due to dehydration.
A patient may be a suitable candidate for surgery if he or she has a life expectancy greater than 2 months. Surgical palliation in advanced cancer patients is a complex issue, and the decision to proceed with surgery should be made by the doctors together with the patient and family members. Medical treatment through continuous SC or lV administration of analgesics, anticholinergic drugs, somatostatin analogues (octreotide) , and antiemetic drugs is a valid method for controlling pain, nausea, and vomiting in patients with inope,rable gastrointestinal obstruction. Percutaneous gatrostomy may be a valuable alternative for the few patients with refractory symptoms who do not respond adequately to pharmacologic measures.
ment of risk factors and outcome. 52~434-437.
Am Surg 1986;
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Journal of Pain and Symptom Management
I93
Pain Therapr and Pczlliative Care Division, National Cancer Institute, Milan, Ita&
Bowel obstruction is a common and distressing outcom in patients with abdominal or pelvic cancer. JR&2 surgery must remain the primary treatmentfor malignant obstruction, it is now recognized that there is a group of patch with advan~d d&ease or poor general ~~~t~o~ who are unfit fm surgq and require alternative m.anagem& to relieve distressing symptoms. A number of treatmnt optiorw are now available j&r the patient with advanced cancer who akte@s intestinal obstmction. This reuitzwexamines the indications fm surgery, the use of n~og~t~ tube and ~~~~~~0~ g~trostomy, and t~p~a~e of drugsfor symp~m co~t~o~~ J Pain Symptom Manage ~994;9:~93-2~~.
Bowel obstruction, advanced and terminal cancer patients
Bowel obstruction
is a common and distressing outcome in the course of malignancies primary within or metastatic to the peritoneal cavity. This complication may arise at any time, but is more likely during the advanced stages of disease. The incidence ranges from 5.5% to 42% in ovarian carcinoma and from 10% to 28.4% in colorectal cancer (Table 1). Table 2 shows the time from diagnosis of cancer to surgery for intestinal obstruction. According to
Address reprint requests to: Carla Ripamonti,
MD,
Pain ‘Iherapy and Palliative Care Division, National
Cancer Institute, via Venezian 1,20133 Milan, Italy. Acceptedfwpublication: September 22, 1993. A version of this paper was originally presented in June 1993 at the meeting “Cancer Care for the 1990s-Supportive Care Issues,” jointly sponsored by Calvary Hospital, Higushi Sapporo Hospital, and Memorial Sloan-Kettering Cancer Center. 0 U.S. Cancer Pain ReiiefCommittee,1994 Published by Elsevier, New York, New York
Gallick and colleagues, the time interval ap pears to be signitlcandy longer for i~~abdominal (mean, 22.4 mo) than extraabdominal (mean, 57.5 mo) tum0rs.r
The most frequent tion are as follows: 1 ~~~~~
causes of bowel obstrun-
occ~~~o~ of the Eunzen. This may be due to enlargement of the primary tumor or omental and mesenteric recurrence, masses, abdominal or pelvic adhesions, or postir~diation fibrosis2 Pancreatic cancer tends to spread directly to the duodenum or stomach, while cancer of the colon spreads to the jejunum and ileum. Prostate and bladder cancer spread to the rectumS5 Tumors at the splenic flexure can cause an obstruction in 49% of cases, while tumors of right and left colon obstruct in 25% of cases.
Incidence
Table I of Bowel Obstruction in Cancer Patients
Authors
Primary cancer
Castaldo et al.24
ov=ly @ary
Tunca et al.” Solomon et al.4O Baines et al.’
R 5.5 25 14.7
Baines et al.’
ovary Colorectal Miscellaneous
Phillips et al.’
Large bowel
16
Kyllonen4r
Colon Rectum
24 4.4
Kyllonen4’ So0 et al.t3
Gynecologic
10” 3”
5
Lund et al.”
0vat-y
14
Beattie et aL4* SteinerY7
ovaly Various
42” 6
QAdvanced cancer.
Only 6% of tumors rectosigmoid junction tion.4 9_.
Vol. 9 No. 3 April I994
Ripamonti
194
of the rectum and cause bowel obstruc-
Intraluminal occlusion of the lumen. This may be due to polypoid lesions due to primary cancer or metastases or annular tumor-al dissemination.
3. Intramural occlusion qf the lumen. This may, for example, be due to infiltration of intestinal muscles (intestinal linitis plastica). 4. Intestinal motility disorders ($wu&obstruction). This may be due to infiltration of the mesentery or bowel muscle and nerves, malignant involvement of the celiac plexus,” or pamneoplastic neuropathy in patients with lung cancer. s Pseudoobstruction is a condition that presents the signs and symptoms of bowel obstruction without a mechanical block. Bowel obstruction is often due to multifactorial causes. In addition to those listed above, the presence of inflammatory edema, fecal impaction, and the administration of constipating drugs may also contribute to the development of intestinal obstruction.
In advanced cancer obstruction is rarely an gradually worsen until ous, and their presence
patients, the onset of acute event. Symptoms they become continuand intensity depends
on the level involved. The symptoms, which are
almost always present, are intestinal colic (reported by 72%-76% of patients); abdominal pain due to distension, hepatomegaly, or tumor masses (I: *i.:orted by 92%) ; and vomiting (68%-100%).7~* Vomiting can be intermittent or continuous; it develops early and in large amounts in gastric, duodenum, and small bowel obstruction, and develops later in large bowel obstruction. Abdominal distension, visible peristalsis, intermittent borborygmi, and anorexia are commonly manifested in patients with bowel obstruction. In cases of complete obstruction, constipation is present for feces and fla.tus. Sometimes overflow diarrhea results from bacterial liquefaction of the fecal material blocked in the sigmoid colon or rectum. Abdominal radiographs taken in supine or standing position are the first investigations to be performed in patients with suspected bowel obstruction. This is done to document the dilated loops of the intestines, or air-fluid interfaces, or both. The study of the small bowel with contrast can distinguish an obstruction due to metastases, radiation bowel damage, or adhesions.”
Treatment w8F-?Y In advanced cancer patients, guidelines for conservative versus surgical treatment are still conflicting. The decision is further complicated by the fact that the causes of the obstruction may be benign (from 6.1% in ovarian cancer to 48% in colorectal cancer) (Table 3).l”
T&L 2 Time from Cancer Diagnosis to Obstruction Authors
Primary cancer
Stage
Tunca et al.**
Ovary
All
Rubin et al.18 Beattie et al.42
CvarY Ovary
All All
29.0 mean
Advanced
19.0 median 15.0 median
Advanced
18.0 median
Spears et al.rO Colorectal Turnbull et al.r4 Carcino matosis Aabo et al.21 Abdominalpelvic
Months 8.3 median 13.1 mean
Vd. 9 No. 3 Apil I994
Management of Bowel Obstruction
Table 3 Rate of Bowel Obstruction due to Benign Causes in Advanced Cancer Patients patients
Primary cancer
NO.
Authors
Benign causes(%) e.--
So0 et al.‘”
64
Gynecologic
Clarke-Pearson et al.43
49
Omly
Tunca et al.11
127
Gallick et al.’
50
Various
26.0
OMty
34.0 6.1 9.4
Osteen et a1.44
66
variuus
31.8
Spears et al. IU
62
Colorectal
48.0
Aabo et al>!
41
Various
12.0
Annest and Jolly”
34
Various
3.0
Not all patients are suitable candidates for surgery. The rate of inoperable patients ranges from 6% to 50% according to different authors.ll-lg The most frequent causes reported in the literature are (a) extensive tumor, (b) multiple partial obstructions, and (c) surgical correction impossible. Benefit from surgery is defined as at least 60 days of survival after operation.2u This defmition, however, does not take into account the well-being of the patient, the presence or absence of symptoms, postoperative complications, or the length of hospitalization. In the study by Lund and colleagues,t* for example, 56% of patients survived 60 days after operation, but 43% of this group manifested intermittent symptoms of incomplete and complete intestinal obstruction until death. Thus, surgery does not always solve the problem of obstruction or eliminate symptoms in advanced cancer patients. In a large percentage of cases, it can lead to further complications (such as wound infections and/or dehiscence, sepsis, enterocutaneous fistula, further obstruction, peritoneal abscess, anastomosis dehiscence, gastrointestinal bleeding, pulmonary embolus, or deep venous thrombosis). Table 4 shows the rates of operative mortality (defined as death from any cause within 30 days of the operation) and morbidity, and the length of survival after surgery for bowel obstruction in cancer patients. Several authors have pointed out the need for prognostic criteria to help doctors in selecting patients who are likely to benefit from surgical intervention. Poor prognostic factors
I95
include (1) intestinal motility problems due to diffuse intraperitoneal carcinomatosis;“,lF’~~” (2) cache&c patients over 65 yr;ls (3) ascites requiring frequeut paracentesis;tzs (4) 10~ serum albumin level;2s (5) previous radiotherapy of the abdomen or pelvis;16.24 (6) palpable intraabdominal masses and liver involvement, or distant metastases, pleural effusion, or pulmonary metastases; 1.t1,ts,22(7) multiple partial bowel obstructions with prolonged passage time on radiograph examination;tt and (8) poor performance statusI
Nasogastric Suction and Intravenous Fluids The usual hospital treatment for symptom control is nasogastric suction and liquid supplementation (“drip and suck”). This is useful in decompressing the stomach and/or intestine, and for correcting fluid and electrolyte imbalance before surgery is performed or while a treatment decision is under consideration. The tube often becomes occluded and requires flushing and/or replacement. During longterm drainage, the nasogastric tube can interfere with cough for clearing pulmonary secretions and may be associated with nasal cartilage erosion, otitis media, aspiration pneumonia, and esophagitis with erosion and bleeding.*” Prolonged nasogastric suction and intravenous fluids for symptomatic treatment of inoperable patients is not recommended. This treatment can create discomfort in patients who are already distressed by previous anticancer and surgical therapies. Such methods are regarded by patients as barriers between them and family members, as they often require hospitalization. An alternative therapy for symptom management has to be found for these patients.
Percutaneous Gastrostomy Percutaneous gastrostomy (PG) introduces a tube into the stomach through the abdominal wall without requiring surgical intervention or regeneral anesthesia. *6S’ This technique quires a brief hospitalization (an average of 4.6 days in one survey). For this reason, PG can be performed safely in advanced cancer patients as a venting procedure for the treatment of nausea and vomiting due to bowel obstruction. to be superior to both It. is widely consideae nasogastric suction and operative gastrostomy for palliation of small bowel obstruction.
Vol. 9 No. 3 ApriE 1994
Ripmmti
196
No. Patients
Authors
Primary cancer
JO-Day mortality (%)
Other operative complications (%I
Survival (mo)
So0 et al.‘s
64
Gynecoiogic
11
15.5
2.5 median
Lund et al.”
25
@Qry
32
32
2.0 median
Rubin et al.tR
43
ovary
9
Castaldo et a1.a4 ClarkePearson et a1.4s
23 49
@ary ovary
13 14
Rrebs and Gopierud’”
93
ovary
Tunca et ai.”
90
Ovary
Piver et al.‘”
60
Ovary
16.5
Beattie et aL4a Walsh and Schofield”
11 36
ovary Various
Aranha et al.“s Aranha et aL4s Osteen et a1.44 Aabo et aLat Chan and Woodru@s Annest and Jollyi Turnbull et ai.t4
40 26 32 41 10 34 89
Various Various Various Various various Various Abdominal
-,
Nor
11.5
6.8 median
43 49
17% lyr 4.5 median
12
12
3.1 median
14
-
7.0 mean
31
2.5 median
9 19
9
7.0 mean 11 median
27.5 46 24.4 40 18 13
22.5 15.0 30 44 44
7.0 4.5 3 4.5 2 4.0 4.5
mean mean median median median mean mean
rcyortcd.
Gemlo and colleague@ reported the experience of 27 inoperable terminally ill patients with abdominal cancer and partial or complete bowel obstruction, A central venous catheter was placed in all patients for administration of 2-3 L of standard electrolyte solution and drugs (opioids, antiemetics, and antispasmotics) when oral and rectal routes of adminis~tion were not viable. In 13 patients, a venting gastrostomy connected to passive drainage was performed to control intractable vomiting due to complete obstruction. All patients were cared for at home by nurses after an average stay in the hospital of 11.2 days. During this period, the patients and their families underwent extensive training in the use of these catheters, infusion pumps, and gastrostomy tubes. There were no complications with gastrostomies. Vomiting was controlled and, with the a~ilabili~ of in~ve~ous (IV) infusion, few patients complained of hunger and none complained of thirst. The average length of survival in these patients was 64 days (range, Q-223 days). P~~~~C#lO~,~
T~~~~t
The few published studies in which symptom control is successfully achieved by administra-
tion of analgesic, anticholinergic, and antiemetic drugs (Tables 5 and 6), without the use of decompressive tube or IV fluids-come from hospices’ or palliative care units.“~*‘~s* Baines and colleagues’ were the first to report the successful control of nausea, vomiting, and pain by means of a pharmacologic approach in 38 patients with bowel obs~~tion due to advanced cancer. Drugs were administered either by mouth, continuous subcutaneous (SC) infusion, or the rectal route. In 68% of the patients, intestinal colic was completely controlled using smooth muscle relaxants, such as scopolamine, atropine, and loperamide. Continuous abdominal pain due to distension, tumor mass, or hepatomegaly was relieved in 89% of the patients using various opioids, namely diamorphine, morphine, and oxycodone. Nausea and vomiting were the most difftcult symptoms to manage, and only 13% of the patients had no vomiting during treatment. Prochlorperazine, chlorpromazine, and haloperidol were effective antiemetics. Metoclopramide was not found to be effective and in fact worsened colicky pain. Thirteen patients somplained of diarrhea and were treated with antidiarrheal drugs, such as loper-
Vol. 9 WQ.3 April 1994
Management of Bowel Obstruction
Table 5
Nausea and Vomiting: Pharmacologic ThemPy 1. Hyoscine bu~lbrom~de 40-120 mg/day subcutane~usly.~~~ lt is possible to increase the dosage until xerostomia and drowsiness are tolerable for the patient. 2. Haloperidol5-15 mg/day subcutaneously.* It can be associated with hyoscine bu~lhromide in the same syringe. 3. Metoclopramide 60-240 mg/day subcutaneously.~Jt It was not used in B&es’s study7 as it may increase colic. In patients with incomplete bowel obstruction, metociop~ide at a dose of 10 mg subcu~neously every 4 hr was the drug of choice.3t 4. IIyoscine hydrobromide 0.3-2 mg/day subcntaneons1y.s 5. Cyciizine 100-150 mg/day subcutaneously or 50 mg every 8 hr rectally, It can be added to prochlorperazine suppositories and to haloperidol subcutaneously. Crystallization may occur at higher dosages or in association with other drugs.3 6. Me~o~imepra~ne 50-150 mg/day subcutane0usly.s It is very effective but it causes sedation and subcutaneous irritation. 7. Prochlorperazine 25 mg every 8 hr rectally. 8. Chlorpromazine 50-100 mg every 8 hr rectally or subcu~eously.3,s7 9. Dimenhydrinate 50-100 mg subcutaneously as needed.2s 10. Dexamethasone 20-40 mg/day,sSs7 3-60 mg/day.B 11. Octreotide 0.2-0.9 mg/day subcutaneousIy.YY~“LI.4~
amide and codeine. The average survival rate of these inoperable patients was 3.7 months after the onset of obstruction. Seven patients (18%) lived more than 7 montiis. This survival rate was longer than that reported by other authors using a similar approach.~,~,3* Ventafridda and colleague@ assessed another pharmacologic approach for the treatment of vomiting and pain in terminal cancer patients with inoperable g~~ointestin~ obstruction. Twenty-two symptomatic patients, who were judged to be inoperable, were treated with the combination of morphine hydrochloride and scopolamine butylbromide as analgesics and h~o~ridoi as an antiemetic. The drugs were administered by continuous SC infusion via a syringe driver or by IV infusion if a central venous catheter had been inserted previously. The period of treatment lasted 2-50 days (mean, 13.4 days; SD = 12.1). Seventeen
197
patients were treated at home and five in the hospital. In both cases, treatment continued until death. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (TO), 2 days after (T2), and 2 days before death {T-2). They showed that there was a significant decrease in the pain score (P c 0.001) on T2 and a further decrease on T-2 (P < 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastrir tube placement. Dry mouth showed an upward trend throughout the observation period (P c 0.05) but was successfully treated by administe~ng liquids by mouth or ice cubes to suck. Drowsiness also presented an upward trend from TO to T-2 (P < 0.001). Only one patient of the 16 who reported thirst required TVhyd~don. These data indicate that vomiting and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administ~tion of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasirgastric tube placement or lV hydration. Fainsinger and colfeaguesss reviewed the charts of 100 consecutive patients dying on the palliative care unit and identified 15 who required medical management of bowel obstruction. Three patients had a nasogastric tube placement for a short period of time
Table 6 Colic@
Pain: Pharmacologic Therapy
1. Hyoscine bu~lbro~de starting with 40-60 mg/ day up to 380 mg/day?ss 2. Hyoscine hydrobromide 0.3-2.0 mg/day subcutaneous1y.s 3. Hyoscine hy~obromide as needed.3
0.S0.6 mg sub~mgu~ly
4. Loperamide 2 mg four times daily.3 5.
Morphine subcutaatotisiy starting with 2.5 mg/hr increasing the dose until relief is achieved.s’
6. Transdermal scopolamine 1.5-3 mg every 3 days.“? 7. Celiac plexus block with alcohol. With all &erapies, gasuokirteticamiemeticslike tuett~ clopramideand doln~ddoxle aud stiIxiulantlax&ves should be discontinued.
198
Ripamonti
during admission to the hospital. A percutaneous gastrostomy was placed in four patients. Medications administered for nausea and vomiting included metoclopramide, dimenhydrinate, haloperidol, hyoscine butylbromide, domperidone, and cisapride. All 15 patient-5 received dexamethasone, and all received hp dradon by hypodermoclysis. The median opioid dose was equivalent to morphine 64 mg/day (range, 21-l&400 mg/day). Medical management for bowel obstruction was required for a mean of 18 days (median, 1’7days; range, 2-41 days). Isbister and colleagues”’ managed 24 patients with advanced abdominal cancer and previous operative or radiologic evidence of intestinal obstruction without surgery. Morphine was administered to control background pain and intestinal colic (mean dose, 9.2 mg/hr) and metoclopramide was used to control vomiting (mean dose, 6.9 mg/hr). A combination of drugs was administered through continuous SC infusion via a syringe driver. The average survival rate after the onset of complete obstruction was 29.2 days. No patient needed a nasogastric tube to control symptoms. De Conno and colleagues”” described the antiemetic role of scopolamine butylbromide administered SC by means of a syringe driver in three women with bowel obstruction due to advanced ovarian cancer. All patients were judged inoperable because of multiple sites of obstruction and were treated with nasogastric drainage and total parenteral nutrition through a central venous catheter. During daily administration of 120 mg, 120 mg, and 80 mg of scopolamine butylbromide, respectively, the quantities of gastrointestinal fluid drained through the nasogastric tube were significantly reduced. Moreover, during the first week of treatment, patients reported that the scopolamine butylbromide provided good relief of colicky pain. Later, morphine hydrochloride was added to the other drugs to control continuous abdominal pain. The nasogastric tube could be removed from all patients following the first week of anticholinergic therapy, which continued until death after 55 days, 172 days, and 54 days, respectively. Dry mouth was reported to be the most important side effect of this treatment, but patients tolerated it by sucking ice cubes and drinking small sips of water.
Vol. 9 No. 3 April 1994
In patients with symptoms due to bowel obstruction, the route of drug administration must be individualized. The oral route is not always possible. Although rectal and sublingual routes are very safe and useful in a home setting,J:! only a few drugs are available for these routes of administration. Those patients with previously inserted central venous catheters have IV access. Other patients can use continuous SC infusion by means of a portable syringe driver, which allows for the parenteral administmtion of different combinations of drugs with minimal discomfort for the patient and ease of use in a home setting. To control continuous abdominal pain, opioids like morphine, hydromorphone, or diamorphine have to be administered SC by a portable pump. Equianalgesic doses must be used when switching from the oral to parenteral route. Doses should be gradually increased until the symptom is controlled. Recently, octreotide, an analogue of somatostatin, has been evaluated as a therapy to control gastrointestinal secretions and vomiting in patients with bowel obstruction.“s*“4 This drug has a powerful inhibitory action on the secretion of gastrin, gastric acid, pancreatic juice, bile flow, and intestinal secretions, and also inhibits gastrointestinal motility and reduces venous splanchnic flow. Several authors have recommended the use of corticosteroids in bowel obstruction because they can reduce peritumoral inflammatory edema and thus improve intestinal passage. No controlled clinical trials have been performed and neither routes of administration nor dosing of these drugs has been standardized. MacDonald”” suggests treatment with either dexamethasone (beginning with 8 mg/day) or prednisone (beginnning with 25 mg every 12 hr); this author recommends gradual dose reduction when the response is positive. Reids” also reported using dexamethasone in initial doses of 20 mg/day for the temporary relief of gastrointestinal obstruction and/or nausea. If no response to dexamethasone occurs with increased doses (5-10 mg/day, SC), Steiner”’ advocates a single IV dose of 25 mg, followed by 100 mg if needed. According to Fainsinger and colleagues, *!) dexamethasone is a very useful agent in managing nausea and vomiting, but its role in preventing progression to complete bowel obstruction is impossible to determine.
Vol. 9 No. 3 April 1994
They administered dexamethasone range of 8 to 60 mg/day.rJ
Management of Bowel Obstmction
with
a
a?& Fainsinger and colleagues% suggest that the two main indications for maintaining hydration in terminal cancer patients are (a) the prevention of dehydration that may cause agitated confusion and (b) prevention of prerenal failure and the resulting accumulation of drug metabolites, such as morphine-Gglucuronide, that may result in complications such as myoclonus or seizure. When relief of obstructive symptoms is obtained through palliative treatment, patients are usually able to drink water and other fluids and to eat small amounts of their favorite foods.7*8*Y’*ss The role of total parenteral nutrition in the management of these patients is controversial.‘G~‘ONo data are available on the survival rates or quality of life in advanced cancer patients treated with this modality. We do not administer total parenteral nutrition in our clinical practice, but, rather, provide fluid by IV infusion (if a central venous catheter was previously used) or by hypodermoclysis2g*sg for control of symptoms due to dehydration.
A patient may be a suitable candidate for surgery if he or she has a life expectancy greater than 2 months. Surgical palliation in advanced cancer patients is a complex issue, and the decision to proceed with surgery should be made by the doctors together with the patient and family members. Medical treatment through continuous SC or lV administration of analgesics, anticholinergic drugs, somatostatin analogues (octreotide) , and antiemetic drugs is a valid method for controlling pain, nausea, and vomiting in patients with inope,rable gastrointestinal obstruction. Percutaneous gatrostomy may be a valuable alternative for the few patients with refractory symptoms who do not respond adequately to pharmacologic measures.
ment of risk factors and outcome. 52~434-437.
Am Surg 1986;
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of the large
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