Atlas of Appendix Cancer - Results of Treatment

Results of Treatment

		No.	No. treatment				Relative
Variables		patients	failures	(%)	p Value		risk (OR)	95% CI

Tumor site
	Appendix	108	38	35
	Colon	8	6	75
	Ovary	2	0
	Unknown	2	2	100	0.014	(b)
	Appendix vs.	108	38	35
	colon	8	6	75	0.05	(a)	6

Preoperative volume
	Volume 1+2	16
	Volume 3	104	46	44	0.00004	(b)	--	0.4, 11.3

Histopathology
	Grade I	94	30	32
	Grade II	26	16	62	0.006	(b)	3.4	1.4, 8.4	(a)

Cytoreduction
	CC-1	90	19	21
	CC-2,3	30	27	90	0.00001	(b)	24.9	4.7, 79.8	(a)

Grade + Resection
	CC-1	74	13	18
	Grade I
	CC-2,3	20	17	85	0.00001	(b)
	CC-1	15	6	40
	Grade II
	CC-2,3	11	10	91	0.014	(a) MH	22.4	8.4, 60.2	(a)

Sex
	Female	40	10	25
	Male	80	36	45	0.047	(a)	2.4	1.04, 5.6

Age
	<65	104	35	34
	>65	16	11	69	0.003	(b)	4.9	1.5, 14.9	(a)

(a)	p<0.05; RR #1
(b)	p<0.01
MH = Mantel - Haenzel test

Table 15

Clinical features of 46 treatment failures in 120 patients with mucinous tumors of peritoneal surfaces. From Sugarbaker PH, Fernandez-Trigo V, Shamsa F: Clinical determinants of treatment failure in patients with pseudomyxoma peritonei (In) Sugarbaker PH (Ed) Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston p 125, 1996.

Figure 43

Sites of treatment failure at second-look surgery in patients with pseudomyxoma peritonei. The most common sites of treatment failure were anterior surface of stomach, small bowel mesentery, surface of colon, especially the residual right colon, suture lines including gastrojejunostomy, colorectal stapled suture lines, and the abdominal incision. All of these anatomic sites would be suspect for recurrence as a result of the methylene blue dye studies performed when chemotherapy is instilled into the closed abdomen. From Zoetmulder FAN, Sugarbaker PH: Patterns of failures following treatment of pseudomyxoma peritonei of appendiceal origin. European Journal of Cancer 32:1727-1733, 1996

Figure 44

Pseudomyxoma spread to the pleural space. If there is full thickness damage to the hemidiaphragm during cytoreductive surgery, adenomatous epithelial cells will gain access to the pleural spaces. If this occurs without special treatments, all of these patients will develop pleural pseudomyxoma over time. If this occurs then the diaphragm should be widely opened so that the surgeon's hand can be thrust into the pleural space. Vigorous manipulation of the pleural surfaces during the heated intraoperative intraperitoneal chemotherapy should be used to eradicate disease from the pleural cavity. In this radiograph pseudomyxoma peritonei had penetrated the diaphragm to cause extensive mucin accumulations on the pleural surfaces.

Figure 45

Kaplan-Meier survival curve of 145 patients by type with pseudomyxoma peritonei treated with cytoreductive surgery and intraperitoneal chemotherapy. Thirty-three patients received four-six cycles of early postoperative intraperitoneal chemotherapy, thirty-three patients received a single cycle of early postoperative intraperitoneal chemotherapy, and thirty-seven patients received heated mitomycin C (HIIC) plus early postoperative intraperitoneal 5-fluorouracil. No significant differences were noted by type of intraperitoneal chemotherapy treatment.

Figure 46

Kaplan-Meier survival curve of 145 patients with pseudomyxoma peritonei. Complete (n=112) versus incomplete (n=33) resection are compared, p=0.0001.

Figure 47

Kaplan-Meier survival curve comparing patients with pseudomyxoma peritonei. Patients with one complete (n=87) versus incomplete cytoreductions (n=27) and patients with multiple surgeries (n=3 1) are shown. Patients required to have additional surgery are not statistically significantly different from those not requiring re-operation.

Figure 48

Kaplan-Meier survival curve showing distribution in pseudomyxoma peritonei patients by histology, p=0.0001. Mucinous tumor grade (MTG) 1 = adenomucinosis, MTG 1.5 = intermediate grade, and MTG 2 = mucinous adenocarcinoma. MTG1 = 113 patients, MTG 1.5 = 25 patients and MTG 2 = 10 patients.

Figure 49

Comparison of laser-mode electroevaporation of carcinomatosis nodules form adenomucinosis nodules. Even though all the cancer visible to the naked eye is resected, the invasive tumor may have persistent disease at the margins of the resection. In a non-invasive implant such as adenomucinosis, the electrosurgical dissection would leave a negative margin. Depth of invasion of the peritoneal surface nodule determines the duration of response to peritonectomy plus perioperative intraperitoneal chemotherapy.

Figure 50

Kaplan-Meier survival curve by prior surgical score. In patients with prior surgical score of 0-2, less than five abdominal regions have been previously explored. In the patients with a heavy prior surgery that are assigned a prior surgical score of three, greater than five abdominal regions had been previously dissected, p=0.0016. Extensive prior surgery before definitive cytoreduction with intraperitoneal chemotherapy jeopardizes the patient's likelihood of long-term survival. Prior surgical score 0-2 = 113 patients, prior surgical score of 3 = 64 patients, (p = 0.0016).

			Projected Survival
		Number	3-Year	5-Year
		of Patients	(%)	(%)	p Value
Survival by the type of
intraperitoneal chemotherapy
(Complete Cytoreduction)
	4-6 cycles	59	89	84	0.65
	1 cycle	42	87	65
	1 cycle with heat	30	100	100

Survival by complete vs.
incomplete cytoreduction
	Complete	138	89	82	0.0001
	Incomplete	32	45	36

Survival by Prior Surgical Score
	0,1,2 (None to moderate)	105	84	84
	3 (Extensive prior surgery)	61	76	56	0.016

Survival by pathology
	Pseudomyxoma	134	86	80
	Pseudomyxoma /
	carcinoma hybrid	32	66	49
	Mucinous carcinoma	50	20	12	0.0001
	Pseudomyxoma, complete
	cytoreduction	114	90	86
	Pseudomyxoma, incomplete
	cytoreduction	20	56	45
	Pseudomyxoma /
	carcinoma hybrid with
	complete cytoreduction	24	75	56
	incomplete cytoreduction	8	33	33
	Mucinous carcinoma,
	complete cytoreduction	14	44	33
	Mucinous carcinoma,
	incomplete cytoreduction	36	6	0	0.0001

Table 16

Summary of prognostic features in patients with appendiceal malignancy showing pseudomyxoma peritonei, intermediate grade pseudomyxoma - adenocarcinoma hybrid or mucinous carcinoma. From Sugarbaker PH, Ronnett BM, Archer A, Averbach AM, Bland R, Chang D, Dalton RR, Ettinghausen SE, Jacquet P, Jelinek J, Koslowe P, Kurman U, Shmookler B, Stephens AD, Steves MA, Stuart OA, White SK, Zahn CM, Zoetmulder FAN. Pseudomyxoma peritonei syndrome. Advances in Surgery 30:233-280, 1997.

	Treatment Group

	Induction IPCT	EPIC	HIIC and	All
Morbidity / Mortality	and EPIC (%)	Only (%)	EPIC (%)	Patients (%)

Anastomotic leak	4.5	3.5	10	6
Small bowel or
gastric fistula	13.6	4.2	8.3	8.7
Bile leak	4.5	1	5	3.5
Pancreatitis	4.5	0	5	3.9
Re-operation for bleeding	0	16.6	5	7.2
All intra-abdominal
complications	27.3	20.8	31.7	26.6
Pulmonary complications	4.5	20.8	1.7	9
Wound dehiscence	0	0	1.7	0.6
Hematologic toxicity,
grade III or IV	4.5	3	6.7	4.7

Overall morbidity	31.8	41.6	35	36.1

Mean duration of ileus	20	21	17	19.3

Mortality	1.6	1.5	5	2.7

Table 17

Morbidity and mortality of cytoreductive surgery with three variants of intraperitoneal chemotherapy. From Sugarbaker PH, Ronnett BM, Archer A, Averbach AM, Bland R, Chang D, Dalton RR, Ettinghausen SE, Jacquet P, Jelinek J, Koslowe P, Kurman RI, Shmookler B, Stephens AD, Steves MA, Stuart OA, White S, Zahn CM, Zoetmulder FAN. Pseudomyxoma peritonei syndrome. Advances in Surgery 30:233-280, 1997.

Figure 51

Clinical pathway for management of gastrointestinal fistulas in patients who have cytoreductive surgery and intraperitoneal chemotherapy. Fernandez-Trigo V, Sugarbaker PH: Diagnosis and management of postoperative gastrointestinal fistulas: A kinetic analysis. Journal of Experimental Clinical Cancer Research 13:233-241, 1994.