The significance of gastrectomy in advanced gastric cancer patients with hepatic metastasis

The significance of gastrectomy in advanced gastric cancer patients with hepatic metastasis

Ibrahim Othman, MD; Hamdy Abdel Hady, MD; MA Hablus MD Department of General Surgery, Tanta University, Tanta, Egypt.

This  study  was designed  to investigate  the role  of palliative  gastrectomy  in  advanced gastric adenocarcinoma  patients having hepatic metastasis  without extra-abdominal  disease at diagnosis.

Patients  and methods:  This study was performed in  General Surgery Department,  Tanta University  Hospitals,  Egypt  on  29 patients  with  advanced  gastric  cancer  having  hepatic metastasis.  Patients  were selected  with histopathologically proven gastric  adenocarcinoma; presence of hepatic metastasis at the time of diagnosis; absence of extra-abdominal  disease and having  a performance  status of 2 or less  on the Eastern  Cooperative  Oncology  Group (ECOG) scale. None had received  prior  chemotherapy  or radiation  therapy   Patients  were categorized into the two groups; Group I, 8 males and 3 females underwent gastrectomy  with subsequent  chemotherapy   Eighteen patients  in group  II, 11 males  and  7 females received chemotherapy alone without gastrectomy. All patients were treated with systemic 5-jluorouracil based regimens.

Results:  The mean  follow-up time  was 258±122  days. The mean  survival of GI and  Gil patients  were 397±59.7 and 173±46.8  days (p > 0.0001).  The mean metastatic  progression­ free survival was 329±54.7  and 141±49.4  days (p > 0.001).  In 11 {38%) of 29 patients  the primary  tumor was removed  (total gastrectomy in 7 and distal gastrectomy  4 patients).  No patient  underwent  liver  resection.  Wound infection  developed  in  one of the patients  of the resection group. He were conservatively treated  One of the patients was reoperated  for minor leakage  from the anastomosis  leading  to intraabdominal collection.  The mean hospital  stay of the first admission for GI and Gil  patients was 13.9 ±6.41 and 4.28±1.41 days respectively (p>O.0001). The Hospitalization index was not different between the two groups. The Ingestion index was significantly higher in GI than in Gil.  Gastrectomy  increased the  survival of the patients regardless to their number and localization of hepatic metastasis. Related risk  factors based on the univariate analysis were serum tumor marker levels (p 0.036), number of hepatic metastasis (p 0.0045), resection of primary tumor (p >0.0001) and the absence of extra hepatic spread (p 0.027).

Conclusion: Despite stage IV patients have poor prognosis, removal of the intact  primary tumor  for gastric  cancer with synchronous hepatic metastasis at diagnosis is associated  with improvement in overall survival and metastatic progression-free survival.

Key words: Gastrectomy, advanced gastric cancer, hepatic metastasis.

Introduction:

Gastric cancer has been described as early as  3000   BC  in  hieroglyphic   inscriptions and papyri manuscripts from ancient Egypt. The first major statistical  analysis of cancer incidence and mortality (using data gathered

in Verona, Italy from 1760 to 1839) showed

that gastric cancer was the most common and lethal cancer. It has remained one of the most important malignant diseases with significant geographical,   ethnic,   and   socioeconomic differences in distribution with approximately

989,600  new  cases and 738,000  deaths  per

year, accounting for about 8 percent of new

Am-Shams] Surg 2014; 7(19):1-10

cancers. 1 Approximately  21,320 patients are diagnosed  annually  in the  United  States, of whom 10,540 are expected to die.2

Despite      some      recent      advances      m

neoadjuvant therapy, studies generally have failed  to show  any improvement  in  overall or relapse-free survival. Surgical treatment remains as the most effective modality in treating gastric cancer3. In the Western world, a potential curative resection is undertaken in less than 40-60% of patients4,5 as compared to 70-85% of patients in Japan6. Palliative surgery   has  traditionally   been  offered  to most remaining patients to relieve symptoms and  maintains  survival.  The benefit  of palliative surgery for stomach carcinoma is controversial.7,8 Questions are commonly raised whether resection should be performed whenever possible and about the survival advantages ofthis resection.

Several  studies  indicate  the  importance of palliative gastrectomy  in Stage IV gastric cancer.9-14 Stage IV gastric cancer is defined according to the American  Joint Committee on  Cancer,  as M1 with  any T or  any  N,l5 in this heterogeneous variety of patients, subgroup analyses are necessary to determine patients who can benefit from surgery.

This study was designed to investigate the

role of palliative gastrectomy in advanced gastric  adenocarcinoma  patients  having hepatic metastasis without extra-abdominal disease at diagnosis.

Patients and  methods:

This study was performed m General Surgery Department, Tanta University Hospitals,   Egypt   during  the   period   from April 2007 to September 2012 on 29 patients diagnosed  with  advanced  gastric  cancer having hepatic metastasis.

Patients     were     selected     according     to

following    criteria:   histopathologically proven gastric adenocarcinoma; presence of hepatic metastasis at the time of diagnosis; absence  of extra-abdominal  disease,  having a  performance  status  of  2  or  less  on  the Eastern  Cooperative  Oncology  Group (ECOG) scalel6 at initial diagnosis and none had received prior chemotherapy  or radiation

therapy.

Full explanation of procedures; possible complications  and patient  consent  were assured before inclusion in the research. The study protocol was approved by the Ethics Committee of General Surgery Department, Tanta University Hospitals. Palliative gastrectomy was decided according to the patient's symptoms and general health, performance  status,  extent  of  the  disease, and feasibility of resection. Patients were categorized  into the two groups.  Group  I, 8 males and 3 females underwent gastrectomy with subsequent chemotherapy. Eighteen patients in group II, 11 males and 7 females received chemotherapy alone without gastrectomy. None of the patients received postoperative         adjuvant        radiotherapy. All   patients   were   treated   with   systemic

5-fluorouracil based regimens.

Follow-up  examinations  were  performed in 3-week intervals during the chemotherapy schedules  and  in  every  three  months thereafter. The follow-up program included clinical examination, hematological analyses, liver function tests, and tumor marker assay (carcinoembryonic antigen (CEA) and CA19-

9),  abdominal  ultrasound  and  chest  x-ray.

Upper digestive tract endoscopy was planned once a year. Abdominal and/or thoracic computed   tomography   was  performed   m cases of suspected recurrence.

Statistical analysis:

Statistical Analysis Quantitative variables were expressed as mean± Standard Deviation. Qualitative      variables      were      expressed as frequency and percent. Quantitative parametric variables were compared between the  two  groups   using  unpaired   student  t­ test, quantitative non-parametric  variables were  compared   using  Mann- Whitney  test. Qualitative  variables  were  compared  using Chi-square  test  or  Fisher  exact  test  (when the criteria for using Chi-square were not sufficient. The power used was 0.80 while the level of significance was 5%.

Results:

Demographics  and  tumor  characteristics

Figure (1): Resection of the stomach.

Figure (2): After complete Resection.

of patients for the GI and Gil are showed in Table (1).  Vomiting, fatigue and weight loss were the main symptoms  of all the patients in this study.  Histologically, 10 patients had intestinal-type adenocarcinoma and 19 had diffuse-type adenocarcinoma.

In 11 (37.93%) of 29 patients the primary tumor    was    removed    (total    gastrectomy in 7 and distal gastrectomy 4 patients). Laparotomy   showed  resection  to  be impossible due to local infiltration of nearby

Figure (3): The specimen showing the tumor.

organs m another 2 patients. They were excluded from this study. No patient had undergone liver resection. Wound infection developed   in   one  of  the   patients   of  the resection  group.  He  was  conservatively treated. One of the patients was reoperated for minor leakage from the anastomosis leading to   intraabdominal   collection.   All   patients were examined by a medical oncologist after their    histopathological    investigation    and were  discharged  from   hospital  after  their

Table 1: Demographics and tumor characteristics of patients for the GI and Gil.

Table 2 .Hospitalization index  and ingestion index.

Table 3: Study  of survival according to liver tumors  in group I

chemotherapy    schedule    was   determined. The mean hospital stay of the first admission for GI and Gil  patients was 13.9 ±6.41 and

4.28±1.41   days  respectively   (p  >0.0001).

The  Hospitalization  index  (the  duration  of

hospital stay relative to the overall survival period)6 was not different between the two groups.   On  the  other  hand,  the  Ingestion index (the duration of the period in which oral intake was maintained relative to the overall

Table 4: Study  of survival according to liver tumors in group II.

Table 5: Study  of effect of resection of primary tumor on survival in both groups.

survival  period)6  was significantly higher  in GI than in Gil Table (2). It was observed  that resection increased the survival of the patients regardless to their number  and localization of hepatic  metastasis Tables (3,4).

The  mean  follow-up time  was  258  ±122

days.   The  mean   survival   of   GI   and   Gil

patients were 397 ±59.7 and 173 ±46.8 days (p

>0.0001).  The  mean  metastatic progression­

free  survival  of the  GI and  Gil  groups  were

329  ±54.7  and  141  ±49.4  days  (p  >0.001). The difference in survival was statistically significant.

The   factors    affecting    overall    survival

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Table 6: Univariate analysis of factors affecting  survival in both groups

in gastric cancer patients who had hepatic metastasis are compared between both groups in  Table (5).  Related  risk  factors   based  on the   univariate  analysis   were   serum   tumor marker levels (p 0.036), number of hepatic metastasis (p 0.0045),  resection  of primary tumor  (p >0.0001) and the  absence  of   extra hepatic spread  (p 0.027)  . These factors  were analyzed with Cox regression analysis  and results are showed  in Table  (6).

Discussion:

In the stage IV gastric carcinomas primary tumor    can   result    in   gastric    obstruction, perforation,  bleeding,   or  excessive ascites. The  aim  of  the  palliative   procedures  is  to manage     those     complications.     Increased survival  may   be   a  secondary  goal  for   a palliative procedure. The benefits of palliative

surgery  in the survival  of the patients  having stage  IV metastasis were indicated in several studies_9-12 The  effect  was  not  identified  in other studies.l 7-19 The reason ofthe different results  in the series  is poor  prognosis in the stage IV gastric carcinomas.  The estimated survival time is too  short  and performing resection or not may have different clinical features. However,  performing the same conditions is clinically impossible. This study was carried out to determine  whether surgical removal ofthe primary tumor provides a better survival and disease  progression. Tumor load reduction diminishes the  metabolic demand by the tumor. In addition,  because  the tumor itself can produce immunosuppressive cytokines, reducing the tumor  load  may also have  an immunologic benefit_20 However, if

a significant  proportion of the tumor  load  is

in-   ams     urg       ;

removed perhaps the disease may be more responsive  to   adjuvant   treatment.21   It can also be seen that gastrectomy was useful for maintaining a longer period  of oral intake.

No hepatic resection was done and all the patients  received chemotherapy. The mean metastatic progression-free survival  ofthe GI and Gil groups were 329 ±54.7 and 141 ±49.4 days (p > 0.001).   Analyses  were  done based on both the number and the localization of the hepatic metastasis. The effect of the presence of solitary  or multiple  metastases on the survival was significantly different. However, bilobar  metastasis was  not determined as an important factor that statistically affected survival.    In   literature  there   were   studies

supporting10,22   and   contradicting7,12  these

findings.

Four signs of incurability were noted: irresectable tumor,  hepatic  metastasis, peritoneal metastasis, and distant lymph node metastasis. The  resectability  rate  decreases as  the   number   of   sites   of   tumor   spread increases.  Survival advantage of resection procedure disappeared when  more  than  two sites  of tumor  spread  were  present.9,23,24 In the  study  of  Kikuchi  et  ai.,25 the  benefit  of resection in the survival  was not presented in the patients  who have both hepatic metastasis and  peritoneal spread.  In the  present  study, all   the   patients    had   hepatic    metastasis. Extra hepatic  spread  was observed only  in 3 patients and resection was not applied to such patients. When their survival was examined according to  overall  survival,  univariate analysis revealed extra hepatic spread  as a negative  factor.

Neither  in this study nor in the others,  the

age of the patient  was determined as a factor that    significantly   affects    survival_l0,11,22

Hartgrink et ai.9 indicated  that  resection  was not  effective  in patients  older  than  70 years with multiple  metastases.

Increased tumor  marker  levels  at the time of diagnosis negatively affect the prognosis. 26

Results  of  the  present  study  supported this finding. However, there was an opposing study.l2

Localization of the  tumor  in the stomach did not affect the survival.lO,ll  Although the

site of the tumor is considered as an important parameter in the study of Kunisaki  et al.,10 neither present study nor the study of Kim et al.22 supports this finding.

The strictest  argument about  palliative resection   versus    other    conservative palliative   procedures is  the  increased ratio of  postoperative  mortality,   morbidity,   and time  of hospitalization_9,10,24 We didn't encounter surgery  related mortality in this study. Complication was observed  in two patients   in  GI.   One   of  these   was  wound sepsis and the other was anastomotic leakage and  localized   peritonitis. The  first  hospital stay in the  GI, was significantly longer  than the other group  but without  significant effect on hospitalization index.  There  were  studies indicating that   palliative   resection   did  not have  a negative  effect  on the  mortality  and

morbidity. 17

In  conclusion,  despite  that  stage  IV patients  have poor  prognosis, removal  of the intact primary tumor for gastric cancer with synchronous hepatic  metastasis at diagnosis is associated  with improvement in overall survival  and metastatic progression-free survival.

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