the study in application of laparoscopic abdominoperineal resection for treatment of low rectal cancer

VIETNAMESE MILITARY MEDICAL ACADEMY PHAM VAN BINH THE STUDY IN APPLICATION OF LAPAROSCOPIC ABDOMINOPERINEAL RESECTION FOR TREATMENT OF LOW RECTAL CANCER Speciality: Gastrointestinal sur

VIETNAMESE MILITARY MEDICAL ACADEMY

PHAM VAN BINH

THE STUDY IN APPLICATION OF LAPAROSCOPIC ABDOMINOPERINEAL RESECTION FOR TREATMENT OF

LOW RECTAL CANCER

Speciality: Gastrointestinal surgery

Code: 62 72 01 25

Ph.D THESIS ABSTRACT

HÀ NỘI - 2013

Scientific supervisors:

1 Assistant Professor, Ph.D: Nguyễn Văn Xuyên

2 Assistant Professor, Ph.D: Nguyễn Văn Hiếu

Thesis reviewer 1: Prof HA VAN QUYET

Thesis reviewer 2: Assoc Prof PHAM DUC HUAN

Thesis reviewer 3: Assoc Prof TRIEU TRIEU DUONG

The thesis was defended at the Council of Military Medical Academy

Due to the above issues, we implemented the study "The study in application

of laparoscopic abdominoperineal resection for treatment of low rectal cancer" with 2 goals:

1 Study lymphadenectomy in laparoscopic abdominoperineal resection for treatment of low rectal cancer.

2 Evaluate results of laparoscopic abdominoperineal resection (LAPR) for treatment of low rectal cancer and some factors associated with survival.

New main scientific contribution of the thesis

Thesis is done at K Hospital – Biggest Cancer Center in Vietnam forstudying lymphadenectomy and evaluating the results of LAPR for treatment oflow rectal cancer

The thesis reports lymphadenectomy results of laparoscopic surgery ensures oncology principles through analysis of number of harvested lymph-nodes The average harvested lymph-nodes is 14.6 per patient Among them, there are 5.5 mesenteric lymph nodes, 5.4 lymph nodes near tumor; 3.7 lymph nodes (LN) of

superior rectal artery The overall rate of lymph node metastasis is 31.11% Stage N1 is 17.78%, N2a is 2.22%, and N2b is 11.11% Metastasis rate of 1 LN station was 14.1%, 2 LN stations is 9.6%, 3 stations is 7.4% Patients treated with

preoperative radiotherapy have less harvested lymph-nodes and lower rate of lymph node metastasis

Thesis reports early results in term of surgery: average duration of surgery is

133 minutes, average blood loss is 13, 6 ml, accident rate is 1.48%, complication rate is 2.8%, no open conversion surgery and no intraoperative and postoperative death The long- term results in terms of oncology is good Average postoperative survival rate is 33.3 months There is no local recurrence and metastasis

Preoperative radiotherapy, lymph node metastasis, stage of disease and age are some factors related to postoperative survival rate

STRUCTURE OF THE THESIS

The thesis consists of 123 pages: 2 introduction pages, 39 background pages,

19 pages for study methods, 24 pages for results, 37 discussion pages, 2 pages for conclusion There are 37 tables, 16 diagrams, 24 pictures, and 149 references, including 30 in Vietnamese, 119 in foreign languages

CHAPTER 1 – OVERVIEW

1.1 Anatomy application in rectal cancer surgery

1.1.1 Anatomical landmarks: The rectum is the last segment of the

gastrointestinal tract connecting with sigmoid colon at the third sacral vertebra and ending at the edge of the anus

1.1.2 Mesentery of rectum: Mesentery of rectum, fat fiber tissue is located within

the limits of the rectal muscle and visceral perineum of pelvis, covering 3/4

circumference of the rectum.

1.1.3 Nerve, blood vessels of the rectum:

The rectum is supplied by 3 main vessel bundles: superior rectal, middle rectal, and inferior rectal artery

Autonomic nerve control rectal secretions, motor nerves control movement

of anal sphincter

1.1.4 The lymphatics of the rectum:

* Lymphatics of mesentery of rectum

* Lymphatics of ischiorectal cavity

* Lymphatics of rectal wall peritoneum

1.2 Histopathology of rectal cancer

1.2.1 Gross appearance: ulcers, infiltration and other type

1.2.2 Micro appearance:

Classification by the World Health Organization (WHO 2000):

Adenocarcinoma accounting for over 98%, carcinoid tumors, lymphoma,

mesenchymal tumors, GIST, Kaposi Sarcoma

1.2.3 The natural progression of colorectal cancer:

Cancer cells spread along the gastrointestinal tract into the submucosal layer.From primary tumor, cancer cells can spread to regional lymph nodes and distant metastases to the liver, lungs, brain as well as invade nearby organs

1.2.4 Evaluating stage of rectal cancer

E Dukes offer the common, simple staging system In 1954, the AJCC established TNM system for stage evaluation for most cancers

1.3 Diagnosis of rectal cancer

1.3.1 Signs and Symptoms:

Abdominal pain, bowel habit change Digital rectal examination is important

to assess rectal tumors

1.3.2 Investigations:

* Colorectal endoscopy: biopsy to identify histopathology

* Diagnostic Imaging: X-ray of the colon with radio-contrast agent has switched to endoscopy, abdominal ultrasound to find out liver, peritoneal

metastasis Endorectal ultrasound assess T stage and N stage CT scanner is

accurate for T stage from 50% to 90%, for N stage from 70% to 80% Pelvis

magnetic resonance imaging (MRI) evaluate T stage and N stage with a sensitivity

of 95%, a specificity of 90% PET-CT find out early postoperative recurrence and distant metastasis

* CEA: Monitoring local recurrence and distant metastasis

1.4 Treatment of rectal cancer

1.4.1 Surgery

1.4.1.1 Principles of radical surgery (R0)

* Remove entire primary rectal tumor

* Remove invaded organs as well as metastatic lesions

* Lymph nodes dissection

1.4.1.2 Surgical types: depend on disease stage, patient condition, the ability of

the surgeon

According to the nature of the treatment, the type of surgery:

* Radical surgery

* Pelvic exenteration surgery

* Palliative surgery

1.4.1.3 The open surgery of rectal cancer:

* Transanal tumor resection

* Low anterior resection

* Abdominoperineal Resection

* Surgery for complications of rectal cancer

1.4.1.4 The laparoscopic surgery of rectal cancer:

Today, with the perfection of surgery skills and endoscopic equipment, all open surgery of rectal cancer is switched to laparoscopic surgery

* Laparoscopic low anterior resection

* LAPR

* Hartmann Surgery

* Sphincter preservation surgery

1.5 Adjuvant treatment for rectal cancer:

* Chemotherapy: improving survival

* Radiotherapy: reducing the incidence of local recurrence and improving disease free survival, so multidisciplinary treatment have become the standard treatment in rectal cancer

1.6 Study situation of LAPR on the world and inVietnam

1.6.1 On the world

The number of LAPR studies are limited

* In 2005, Aziz.O review literature from 1993 to 2004 There are 22 studies with 2071 patients, only 8 studies mentioned laparoscopic lymphadenectomy in LAPR

* According to major report by Wiley Publishers in 2008, there are 33 clinical trials from 1988 to 2007 on 46 medical journals, among them 6 studies on

lymphadenectomy in LAPR, 12 studies on 5 year survival in LAPR with 3346 patients.

* Lourenco.T, Health Research Institute of Britain in 2008 review

laparoscopic surgery compared with open surgery on 4500 patients from 1997 to

2005 on the world 12 studies mentioned lymphadenectomy but did not regard to LAPR

Some larger ongoing study on LAPR:

* Study of Japan Cancer Research Group will finish by 2014

* European Colorectal Cancer Research Group will finish by 2017

* Study of United States Cancer Surgeon Association is going to report in 2013

1.6.2 In Vietnam

From 2003 to 2012, mainly focusing on perfecting surgical techniques such

as removal of entire mesentery of rectum, preservation of nerves and urogenital fuction Recently there have been some researches on LAPR But these has not really focused on the role of lymphadenectomy and postoperative results

Thus LAPR still need further studies to confirm that LAPR is a standard option in the treatment of low rectal cancer

CHAPTER 2 - SUBJECTS AND METHODS 2.1 Study subjects: Patients with low rectal cancer at K Hospital from 01/01/2009

to 31/12/2011 underwent curative LAPR, follow up to 30/06/2012

2.2 Research Methodology

2.2.1 Methods: prospective descriptive study (cross-sectional non-control).

2.2.2 The formula for calculating sample size: The minimum sample size was

calculated as following:

n = (1.96) 2 x 0.056 x 0.944 / (0.05) 2 = 81.2 patients

According this above formula, minimum sample size are 82 patients

2.3 The study targets: the clinical, pathological, investigation characteristics

2.3.1 The clinical characteristics

2.3.2 The pathological, investigation characteristic

2.4 LAPR and lymphadenectomy process

2.5 Assessment results

2.5.1 Lymphadenectomy results

* Total number of harvested lymph-nodes on 135 patients

* The average number of lymph nodes per 1 patient (mesenteric lymph nodes, lymph nodes near tumor, lymph nodes of superior rectal artery)

* Overall rate of lymph node metastasis, metastasis rate of LN stations, LN stages

* The average number of lymph nodes per 1 patient and lymph node

metastasis rate of patients with and without receiving preoperative radiotherapy

2.5.2 Early Results

* Operation time, estimated blood loss

* The surgical complications: bleeding, urinary, intestinal damage

* The postoperative complications: bleeding, intestinal obstruction,

infection, abscesses, bladder paralysis

* Time using IV or IM algenesthesia, bowel peristalsis, and length of

hospital stay

* Mortality due to surgery: in 30 days after surgery

2.5.3 Delayed results and some related factors

2.5.3.1 The postoperative survival by Kaplan-Meier

Postoperative follow up every 3 months for first year, followed by every 6 months in next 2 years, and every year from the fifth year

Results of treatment at the end of the study:

* Number of alive patients, died patient

* Rate of local recurrence, distant metastasis, trocar holes recurrence

* The median survival

* The average survival at 6 months, 12 months, 24 months, 36 months

2.5.3.2 Analysis on factors related to survival

* Age ≤ 60 years and> 60 years old

CHAPTER 3 – RESULTS

3.1 General Characteristics

* Age, sex: 135 patients with mean age 55.3 69 male, 66 female Rural: 98 Urban: 37

-* The average time from onset of symptoms until having diagnosis is 3.8 ± 1.2 months, 14.07% of patients having a previous operative scar.

3.2 Clinical Characteristics

* Symptoms: abdominal pain, tenesmus, blood mixed with stool accounting for 97.78%

* Digital rectal examination: 1 to 3cm distance from tumor to anus

accounting for 94.81% , 68.89% tumors involved 1/2 to 2/3 of the circumference; limited motion tumors accounting for 35.56%

* Endorectal Ultrasound: 18.5% of patients were done 100% of patients is stage T3, 40% patients had lymph node metastatic image

* The histopathology results: 100% tumors are invasive, 97.04% tumors have 1 to 3cm distance from tumor to anus, tumor size from 2 to 5 cm accounting for 95.6%; serosa invasive tumors accounting for 57.78% , and T4 stage is 42.22%

3.4 Treatment before and after surgery:

35.55% of patients underwent preoperative radiotherapy, 42.22% of patients received adjuvant chemotherapy.

3.5 Lymphadenectomy Results

Table 3.15: Average number of lymph nodes classified according to dissection sites.

Radiotherapy No Radiotherapy Total

- The average number of lymph nodes near tumor was 5.4 (group with

radiotherapy: 4.7, group without radiotherapy: 5.8), mesenteric lymph nodes was 5.5 (group with radiotherapy: 4.7, group without radiotherapy: 6.0), lymph nodes

of superior rectal artery was 3.7 (group with radiotherapy: 2.7, group without

radiotherapy: 4.2)

Table 3:16: The rate of metastasis lymph node classified according to stations.

Metastatic lymph nodes Number of patients

(n)

Percenta

ge %Metastasis rate of 1 LN station 19 14.1Metastasis rate of 2 LN stations 13 9.6Metastasis rate of 3 LN stations 10 7.41Metastasis rate (at least 1 in 3 stations) 42 31.11

Comment:

The overall rate of lymph node metastasis was 31.11%, in which 7.4% of patients have metastatic lymph nodes in all three stations

Table 3:17: The rate of lymph node metastasis

Histology Number of patients (n) Percentage%

No metastatic lymph nodes (N0) 93 68.89

From 1-3 positive lymph nodes (N1) 24 17.78

From 4-6 positive lymph nodes (N2a) 3 2.22

More than 6 metastatic nodes (N2b) 15 11.11

Comment: The rate of lymph node metastasis is 31.11%, Almost from 1-3 positive lymph nodes (N1: 17.78%)

Table 3:18: Lymph node metastasis rate of patients with and without receiving preoperative

radiotherapy

Histology

Radiotherapy

Noradiotherapy Total p

N1/N2 9 18.8 33 37.9 42 31.11

<0.05N0 39 81.3 54 62.1 93 68.89

* The average duration of surgery was 113 minutes (SD 20.87)

* The average blood loss was 13.6 ml (SD 12.21)

* Complications in operation: 1.4% (intestinal bladder, perforation), no opensurgery conversion

* Time using IV or IM algenesthesia: ≤ 2 days

* The time to return of bowel function was: 33.14 ± 4.4 hours

* Postoperative Complications rate was low: 2.8%, 1 case must be operated again due to postoperative bowel obstructions

* The average hospital stay was: 7.38 days (SD 1.82)

* There were no deaths due to surgery

3.7 Long-term results and some factors related to survival time

Until 30/06/2012, 116 over 135 patients are alive (85.9%) There is no local recurrence and distant metastasis, 19 patients were died (14.1%).

Table 3:28: The median overall survival

Mean (months)

n X SD 95% CIMedian overall survival

135 33.33 1.00 (31.37 –

35.28)

Comment: The median survival is 33.33 months

Chart 3.12: The median survival

Table 3:29: Overall survival 6 months, 12 months, 24 months, 36 months (Kaplan

A number of factors related to survival time:

* There is no statisticaly significant difference between group of patients <

60 year old and group > 60 year old (p > 0,05)

* The median overall survival in group with lymph node metastasis was 28.42 months lower than group without lymph node metastasis (33.06 months) (no statisticaly significant difference, p > 0.05)

* The median overall survival in group with preoperative radiotherapy was 33.34 months higher than those without preoperative radiotherapy (30.74 months), statisticaly significant difference (p < 0.05)

* The median overall survival in group with stage III was 28.42 months lower than group with stage II (33.06 months), no statisticaly significant difference(p > 0,05)

CHAPTER 4 – DISCUSSION

4.1 General Characteristics

* Age and gender: results of the age and sex of this study are similar to otherrecent studies

* Geography factor (urban or rural areas) do not affect on the study results

4.2 The clinical and investigations:

4.2.1 Clinical

* Time from onset of symptoms to hospital admission was 3.6 ± 1.2 months.The others in Viet Nam was later (4.5 to 6 months)

* Symptoms: abdominal pain, tenesmus, accounting for 97.78% While other authors report mucus stool, difficult defecation.

* Digital rectal examination: There are 48 patients with limited motion tumors treated with preoperative radiotherapy Efron reports accuracy of digital rectal examination is 80%

* CTscanner is not high value in evaluation T stage (25% to 80%), and N stage (35% to 70%) Because of this weakness, the number of patients given CTscanner was not many (14.8%)

* Magnetic resonance imaging (MRI): According to many studies value of MRI in evaluation T stage is 85% - 95%, and N stage is 84% Among 135 given MRI, 27.41% of patients with stage III, 72.59% patients with stage II, that reflects the randomization of this study

* Endorectal Ultrasound: Recent studies show that the diagnostic value of endorectal ultrasound is 60% - 90%, N stage is 64% - 83% , especially in sphincterassessment, accuracy up to 90% However, the number of patients in this study given endorectal ultrasound was still small (18.5%), so we do not comment much

on endorectal ultrasound

4.3 Evaluating lymphadenectomy results of LAPR

Lymphadenectomy is a criteria in cancer surgery, it is an important

prognostic factor In laparoscopy, how to lymphadenectomy in cancer principles: