The influence of sarcopenia and cancer cachexia on recovery of gastric and colonic surgery

The Netherlands will encounter a disproportionate increase of an ageing
population. The number of elderly cancer patients is concomitantly increasing
in the Netherlands, as is the number of the elderly undergoing surgical
treatment. Fifty percent of patients with colorectal cancer are above age 70.
While survival of all cancer types is increasing, improvement of cancer outcome
has been relatively limited in older patients, which can at least partly be
explained by an increased postoperative mortality. Recovery after surgery plays
a crucial role in cancer treatment in terms of survival, treatment response and
morbidity. *Frail* elderly have a 3-fold increased risk of postoperative
mortality, while *non-frail* elderly have just a minimally increased risk.
There are many controversial issues surrounding the definition of frailty and
on its mechanisms leading to postoperative morbidity and mortality. The
syndrome of frailty is a state of increased vulnerability towards stressors in
older individuals, leading to an increased risk of developing adverse health
outcomes. However, the definitions and biological characteristics of frailty
are subject to debate. Weight loss, low muscle strength, reduced physical
activity, exhaustion, and slowed walking speed are symptoms of a physical
definition of frailty, whereas comorbidity, polypharmacy, physical functioning,
nutritional and cognitive status, depression and social support are a more
multidimensional tool to assess frailty. Skeletal muscle wasting is an element
of frailty in both definitions. Preliminary results of our research group
indicated that sarcopenia in elderly cancer patients undergoing colorectal
surgery is associated with increased postoperative morbidity. Moreover, results
of this study showed increased intestinal damage in several patients undergoing
colonic resection. These patients had an increased risk of developing severe
postoperative complications. Therefore, we hypothesize that sarcopenia and/or
cancer cachexia negatively affect postoperative recovery after surgery for
malignancy. To find treatment strategies for these adverse effects, it is
necessary to study skeletal muscle changes in these patients and how these
changes can affect postoperative recovery.

1) To investigate what changes are present in skeletal muscle tissue of elderly
gastric and colonic cancer patients (>80) compared with younger gastric and
colonic cancer patients (<60) and compared to elderly controls and younger
controls.
2) To investigate how these changes affect important elements of gastric and
colonic healing.

The following patients will be enrolled in the current study:
15 patients undergoing gastric surgery for malignancy older than 80 years of
age,
15 patients undergoing gastric surgery for malignancy younger than 60 years of
age,
15 patients undergoing colonic surgery for malignancy older than 80 years of
age,
15 patients undergoing colonic surgery for malignancy younger than 60 years of
age,
15 patients undergoing abdominal wall incisional hernia repair older than 80
years of age,
15 patients undergoing abdominal wall incisional hernia repair younger than 60
years of age.
These study groups give the opportunity to investigate the effects of
sarcopenia (caused by age) as the effects of cachexia (caused by cancer). It is
hypothesized that cachexia will be most prevalent in patients with gastric
cancer, to a lesser extent in patients with colonic cancer and not prevalent in
patients with incisional hernia.

Muscle biopsies
In all patients, a biopsy of the rectus abdominis muscle will be taken
peroperatively. After skin incision and dissection of subcutanous fat, the
anterior rectus sheath will be opened and a muscle biopsy of approximately 1,5
cm³ will be taken. Surgery time will be extended less than one minute and no
extra incisions are needed. Opening the rectus sheath is part of routine care
in gastric surgery, colonic surgery and hernia repair. The muscle tissue will
be snap frozen immediately in liquid nitrogen cooled isopenthane en stored at
-80ºC until batch analysis in the laboratory of the department of general
surgery (MUMC).

Fat biopsies
Inflammation of fat tissue and loss of fat tissue are important aspects of
cancer cachexia. Therefore in all patients, a biopsy of fat tissue will be
taken peroperatively. After skin incision, a subcutaneous fat (SF) biopsy of
approximately 1,5 cm³ will be taken. After opening of the muscle layers and
muscle biopsy, a visceral fat (VF) biopsy of approximately 1,5 cm³ will be
taken of the omentum. Fat biopsies can be taken without blood loss. Surgery
time will be extended less than one minute and no extra incisions are needed.
The fat tissue will be snap frozen immediately in liquid nitrogen cooled
isopenthane en stored at -80ºC until batch analysis in the laboratory of the
department of general surgery (MUMC).

Colonic tissue
In patients undergoing colonic surgery, a small part of the specimen that is
resected will be removed for the current study. In left hemicolectomies and
sigmoid resections, the most proximal 2 cm of the specimen will be taken, and
the most distal 2 cm of the specimen will be taken in right hemicolectomies.
The tissue will be snap frozen and stored at -80ºC until batch analysis in the
laboratory of the department of general surgery (MUMC).

Gastric tissue
In patients undergoing colonic surgery, a small part of the specimen that is
resected will be removed for the current study. 4 cm² of gastric wall will be
taken from the proximal part of the specimen. The tissue will be snap frozen
and stored at -80ºC until batch analysis in the laboratory of the department of
general surgery (MUMC).

Venous puncture
Venous blood will be collected in EDTA vaccuum tubes (5 milliliter per sample)
prior to surgery, one day postoperatively and three days postoperatively. This
does not include extra venous puncture for study purposes, as standard care
includes venous puncture at the specified timepoints in all patients. Blood
samples will be centrifuged and stored at -80ºC until batch analysis in the
laboratory of the department of general surgery (MUMC).

The rectus abdominis muscle biopsy and fat biopsies are the only burden
associated with participation. The rectus abdominis muscle layer is dissected
in gastric surgery, colonic surgery and abdominal hernia repair surgery as part
of standard care. Access to subcutaneous fat and visceral fat is possible
without extra incisions. The biopsies might increase postoperative pain
slightly.