According to the Cancer Registration, in 2009, colorectal cancers remain the second most common cause of cancer death in Hong Kong.
Survival is, most of the time, related to the extent of the disease and the presence of liver metastases is one of the major determinants of patient survival.
About 25% of new cases of colorectal cancers will be discovered to have liver metastases upon presentation (synchronous liver metastases) and up to 50% will develop liver metastases during the course of their disease (metachronous liver metastases).
It is agreed that aggressive multimodal therapy for colorectal liver metastases can extend the survival and improve the quality of life of most patients with liver metastases.
For liver metastases, surgery is the treatment of choice and the 10-year survival rate can reach over 20% in various centres. Liver
resection, when feasible, is the only treatment associated with long-term survival.
A multidisciplinary approach, including systemic chemotherapy, targeted therapy and innovative surgical techniques has enabled a larger proportion of patients to benefit from potential curative treatment. With improvements in surgical and anaesthetic techniques, as well as postoperative care, liver surgery has become a safe procedure in experienced centres.
Selection of surgical candidates
All patients will benefit from evaluation by a multidisciplinary team comprising surgeons, medical oncologists, radiologists, nurses and social workers. Consensus will be reached during the combined assessment and delay in treatment can be minimised. In identifying surgical candidates, evaluation will be made on
patient’s fitness for operation
anatomic and functional determination of tumour resectability
individual’s tumour biology
Evaluation of fitness for operation
A careful evaluation of a patient’s physiologic capability to stand liver resection is crucial. It is generally agreed that patient’s age alone should not be considered a contraindication for surgery.
Anatomic and Functional determination of resectability
Resectability is being defined by American Hepato-PancreatoBiliary Association Society of Surgery of the Alimentary Tract/Society of Surgical Oncology in 2006 as “an expected margin-negative resection resulting in preservation of at least 2 contiguous hepatic segments with adequate inflow, outflow, and biliary drainage with a functional liver remnant (FLR) volume of more than 20% (for healthy liver) ”.
A liberal use of CT volumetry is encouraged in assessing the safety of liver resection – future liver remnant (FLR) approaching 20% for patients with normal liver, 30 - 40% for patients with underlying liver disease.
The criteria of resectability have shifted from basing on morphologic characteristics of metastases to new criteria that based on whether both intra-hepatic and extra-hepatic disease can be completely resected or not.
Analysis of Tumour biology
In assessing the tumour biology, one tries to see whether the patient’s disease favours a more indolent or a more aggressive behavior.
Factors include stage of the primary disease, tumour histology, disease-free interval, number and distribution of liver metastases, response to chemotherapy, rate of growth of liver metastases, rate of increase in CEA level as well as presence and extent of extra-hepatic disease.
Controversies in resection of liver metastases
Timing of chemotherapy to surgery
Potential benefits of pre-hepatectomy chemotherapy include the possibility for downstaging liver metastases, in vivo testing of chemotherapeutic efficacy and early exposure of subclinical microscopic metastases to systemic therapy.
The downsides of preoperative chemotherapy are largely related to liver toxicities which might be clinically relevant. There are reports of association of the hepatotoxicity from chemotherapy with an increase in perioperative complications.
The extent of resection after downstaging with chemotherapy has been a problem – the outcome and patterns of recurrence are ill-defined in patients who have complete radiographic response to neoadjuvant therapy.
It is agreed that liver resection should be performed as soon as the liver disease becomes resectable.
Synchronous liver metastases
Potential benefits of simultaneous liver resection and resection of the primary colorectal cancer include avoidance of a second laparotomy and anaesthesia, and reduced time to initiation of adjuvant chemotherapy.
On the other hand, risks of simultaneous resection will largely be related to the magnitude and complexity of the combined operation.
Practice is different in different centres and the decision is usually tailor-made by surgeons & medical oncologists.
Bilobar liver metastases
Bilobar liver metastases, itself, is no longer an absolute contraindication to resection. Extended liver resection, 2-stage liver resection and combined liver resection and ablation are possible ways to get over the extent of liver disease.
For patient with insufficient liver reserve, portal vein embolization may be employed to increase the size of the future liver remnant to allow safe extended liver resection.
Again, with the advent of more effective systemic therapies, extra-hepatic disease is no longer an absolute contraindication to surgery, though surgery should not be the first line of treatment in patients with wide-spread metastases.
An assessment of tumour biology is critical in selecting patients for surgery for the hepatic and extra-hepatic diseases. It is not advisable to operate for hepatic or extra-hepatic metastases in the presence of disease progression on chemotherapy.
The goal is to achieve a liver resection with negative margins and to preserve 2 contiguous liver segments, as well as ensuring an adequate future liver remnant to avoid liver failure.
Anaesthesiologist’s support is paramount as it is now a standard practice to perform liver resection with a low CVP.
During the operation, the surgeon will first look for intra-abdominal metastases not detectable with preoperative imaging. Next an intra-operative ultrasound of liver is performed to confirm resectability. If all these are satisfied, liver resection will then be carried out.
There are new tools and maneuvers in performing liver parenchymal transection in addition to the traditional finger-fracture technique. However, none of these tools is proven to be superior, so far.
There are centres performing laparoscopic liver resection or ablation for patient with colorectal liver metastases.
Moving on from the first colorectal hepatic metastasectomy in 1943, by Cattell at Lahey Clinic, to present, a dramatic improvement in the outcome of surgery for liver metastases was seen. The improvement is mainly a result of better understanding of liver anatomy, better preoperative imaging, intraoperative ultrasonography, low CVP anaesthesia together with a better perioperative support.
Although, undoubtedly, the advancements in local and systemic therapies have improved the prognosis of colorectal liver metastases, liver resection remains the cornerstone of definitive treatment with regard to disease-free and overall survival.
There is a trend for a more aggressive surgical approach in this era of better systemic therapies and it says for the need of a more dynamic relationship between surgeons, medical oncologists and intervention radiologists. It is for this reason; a multidisciplinary team approach is the way to go in the management of colorectal liver metastases.
The patient was a 7 year old girl. She complained of nocturnal enuresis since early childhood. Detailed history reviewed the girl had daytime incontinence as well. Physical examination showed clear fluid effluxing from vagina. Bladder diary documented normal voiding pattern and volume, with continuous urinary incontinence not relating to urination. The clinical picture was indicative of ectopic ureter draining into vagina.
The diagnosis was confirmed with subsequent imaging study including ultrasound and magnetic resonance urography, which showed left duplex kidney with poor function upper pole draining into vagina via an ectopic ureter. The patient underwent laparoscopic left upper pole heminephroureterectomy
and recovered uneventfully. She remained asymptomatic after the operation.
Nocturnal enuresis, or bedwetting, is a common clinical problem in children. Monosymptomatic nocturnal enuresis describes bedwetting in children with no daytime urinary symptoms to suggest underlying voiding dysfunctions or structural abnormalities. However, there is a gray zone between monosymptomatic nocturnal enuresis and nonmonosymptomatic nocturnal enuresis. After thorough evaluation many children assumed to have monosymptomatic nocturnal enuresis are found to have nonmonosymptomatic nocturnal enuresis. Furthermore, the pathogenesis overlaps between the two conditions. Thus, evaluation of and treatment for the two entities have many similarities.
Comorbid conditions often have a central role in the pathogenesis and potential therapy resistance of enuresis. Paramount among these conditions are constipation, obstructive sleep apnea, and neuropsychiatric disorders such as attention deficit hyperactive disorder. These conditions may decrease the chance of successful therapy.
Patients with underlying structural abnormalities may also present with enuresis, such as spina bifida occulta, posterior urethral valve or ectopic ureter etc.
Ask specifically about daytime incontinence and symptoms such as urgency, holding maneuvers (standing on tiptoe, pressing the heel into the perineum etc), a weak stream and the need to used abdominal pressure to pass urine. Patients with weak stream and need to use abdominal pressure to pass urine should be referred for further assessment +/- investigations such as urodynamic study.
Since bladder and bowel function are closely interrelated, questions on bowel function are closely interrelated, questions on bowel habits should also be posed. If concomitant constipation is not treated first, it may be difficult to get the child dry.
Ask for any history or symptoms of urinary tract infection.
Some questions on general well being are indicated. Has the child lately become tired or lost weight? Children may suffer from diabetes or kidney disease and present with nocturnal enuresis.
An estimation of fluid intake in needed. Children with polyuria due to diabetes or kidney disease obviously need further investigation and desmopressin therapy may be dangerous in children with habitual polydipsia Fluid intake is best estimated with a bladder diary.
The presence or absence of heavy snoring or nocturnal sleep apnea in a bedwetter can be relevant information since some become dry after upper airway obstruction is relieved.
Physical Examination and Other Primary Examinations
Physical examination in a child with monosymptomatic enuresis is usually normal. Examination of the lower back and external
genitals is mandatory in all children with a history of urinary tract infection or nomonosymptomatic nocturnal enuresis.
A urine dipstick test should be performed if possible. Glycosuria means that diabetes mellitus must be immediately excluded and proteinuria in repeat samples should prompt investigations for kidney disease.
Routine ultrasound of the kidneys and upper tract is not warranted, except in situation in which congenital abnormality is suspected e.g.ectopic ureter or duplex kidney. However, ultrasound measurement of bladder wall thickness and assessment of the bladder volume and emptying efficiency would be useful information for subsequent management.
Completion of a frequency-volume chart or bladder diary is recommended
It provides objective data that may support the history
It helps detect children with nonmonosymptomatic nocturnal enuresis
It detects children who require extra evaluation
It detects children with polydipsia
While general advice should be given to all bed wetting children, active treatment should usually not be started before age 6 years.
General lifestyle Advice
Suggest the family to keep a calendar of dry and wet nights. This provides a baseline to judge the effect of therapeutic interventions and has an independent therapeutic effect (grade Ib evidence).
Children with nocturnal enuresis should be counseled to void regularly during the day, and always at bedtime and on awakening.
Liberal water and solute intake during the day is recommended. Evening fluid and solute intake should be minimized.
If there is any sign of constipation, this should be treated.
If the parents have the habit of waking the child at night to go to the toilet, they should be informed that this is allowed but not needed and would only help for that specific night, if at all.
Therapy in uncomplicated cases
Besides general advice, there are currently two valid first line therapies, including the enuresis alarm and desmopressin.The alarm is best for well motivated families and for children without polyuria but with low voided volume. Desmopressin is best suited for children with nocturnal polyuria and normal bladder reservoir function.
Evaluation and Treatment in therapy Resistant Children
Children with enuresis who are nonresponders to the 2 firstline therapies deserve further evaluation. In therapy resistant children the completion of a frequency-volume chart is mandatory and constipation should be excluded. It is also prudent to perform ultrasound to assess bladder wall thickness which indicates probable underlying detrusor overactivity. More invasive test such as urodynamic study should be considered in refractory NE patients especially those with abnormal ultrasound findings.
Concomitant psychiatric disorders could be reason for therapy resistance. These children may need psychological screening.
Dr Cheung Sing Tak, Gloria Specialist in Paediatric Surgery, Union Hospital