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Pseudomyxoma Peritonei: Aspects of Natural History, Learning Curve, Treatment Outcome and Prognostic Factors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous peritoneal metastasis (PM). Different loco-regional treatment strategies, i.e. debulking surgery and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), have changed the prognosis for these patients. CRS is an aggressive surgical procedure with a long learning curve. PMP exists in different types; how many depends on which classification is used.

The aims of this thesis were to investigate the time-frame of PMP development from an isolated appendiceal neoplasm, examine the learning process for CRS, evaluate the differences in treatment outcome between debulking surgery and CRS in combination with HIPEC, to evaluate a more detailed PMP classification and to investigate particularly interesting new cysteine-histidine (PINCH) protein as a prognostic factor for PMP.

Retrospectively 26 PMP patients were identified as having had an appendectomy with a neoplasm in the appendix but with no evidence of PM at the appendectomy. They were treated for PMP within a median of 13.1 months (3.8-95.3) after the appendectomy. No difference was seen between the types of PMP regarding the time to a clinically significant development of PMP and how much tumour was found at treatment. CRS is a highly invasive treatment and stabilization in the learning curve was seen after 220±10 procedures. Patients treated with CRS+HIPEC had a better 5-year overall survival (OS) than patients treated with debulking surgery, 74% vs. 40%. CRS increased the rate of complete cytoreduction from 25% in patients treated with debulking surgery to 72%. The new four-grade PMP classification showed very good inter-rater agreement between two independent pathologists and a difference in survival rates was observed between the different grades. A positive PINCH staining was recorded in 83% of the tumours and that was associated with poorer survival.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 896
Keyword [en]
Pseudomyxoma peritonei, Natural history, Learning curve, Cytoreductive surgery, Debulking surgery, Treatment outcome, Prognostic factors, PINCH
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-197434ISBN: 978-91-554-8651-8 (print)OAI: oai:DiVA.org:uu-197434DiVA: diva2:615111
Public defence
2013-05-25, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2013-05-03 Created: 2013-03-25 Last updated: 2013-08-30
List of papers
1. The natural history of pseudomyxoma peritonei- the early phase
Open this publication in new window or tab >>The natural history of pseudomyxoma peritonei- the early phase
(English)Manuscript (preprint) (Other academic)
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-197430 (URN)
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2013-08-30
2. Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
Open this publication in new window or tab >>Cytoreductive surgery in pseudomyxoma peritonei-aspects of the learning curve
Show others...
2013 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 8, 930-936 p.Article in journal (Refereed) Published
Abstract [en]

Background: Cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy is a highly invasive treatment of peritoneal metastasis and requires many surgical procedures before mastering. The aim of this study was to estimate how many procedures are needed before stabilization can be seen in surgical outcome (R1 surgery, adverse events and bleeding) in patients with pseudomyxoma peritonei (PMP). Patients and methods: All 128 patients with PMP who were treated with CRS alone or CRS plus perioperative intraperitoneal chemotherapy between 2003 and 2008 at the Uppsala University Hospital, Uppsala, Sweden, were included. The learning curve was calculated using the partial least square (PLS) and cumulative sum control chart (CUSUM) graph. Two groups were formed based on the results of the learning curve. The learning curve plateau was considered the same as the stabilization in the CUSUM graph. Group I consisted of patients included during the learning period (n = 73) and Group 11 of patients treated after the learning period ended (n = 55). Comparisons between the groups were made on surgical outcome, survival and adverse events. Results: Stabilization was seen after 220 +/- 10 procedures. A higher occurrence of R1 surgery was seen in Group H (80%) compared to Group I (48%; P = 0.0002). Overall survival increased at four years after surgery in Group H compared to Group I (80% vs. 63%; P = 0.02). Conclusion: CRS plus perioperative intraperitoneal chemotherapy is a highly demanding procedure that requires more than 200 procedures before optimisation in surgical outcome is seen.

Keyword
Cytoreductive surgery; Pseudomyxoma peritonei; Learning curve; Survival
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-197433 (URN)10.1016/j.ejso.2014.03.001 (DOI)000339533700004 ()24656455 (PubMedID)
Funder
Swedish Cancer Society, 10-0561 CAN 2010/569
Available from: 2013-04-08 Created: 2013-03-25 Last updated: 2017-12-06Bibliographically approved
3. Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
Open this publication in new window or tab >>Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
Show others...
2012 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, 962-968 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.

PATIENTS AND METHODS:

Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.

RESULTS:

One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).

CONCLUSIONS:

CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-181434 (URN)10.1016/j.ejso.2012.07.009 (DOI)000309787600012 ()22809859 (PubMedID)
Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
4. Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
Open this publication in new window or tab >>Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
Show others...
2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, 1443-1448 p.Article in journal (Refereed) Published
Abstract [en]

Aim:

The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.

Materials and Methods:

Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.

Results:

The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).

Conclusion:

The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.

Keyword
Pseudomyxoma peritonei, histopathology, PINCH, protein expression, cytokeratin 7, Ki-67
National Category
Medical and Health Sciences Basic Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-173640 (URN)000302492600043 ()22493383 (PubMedID)
Available from: 2012-05-09 Created: 2012-05-02 Last updated: 2017-12-07Bibliographically approved

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