When you need pancreas cancer surgery even without definite diagnosis of pancreas cancer?? What does international study group on pancreas cancer say??

When you need pancreas cancer surgery even without definite diagnosis of pancreas cancer?? What does international study group on pancreas cancer say??

Surgery (PANCREATODUODENECTOMY ) provides the best chance for a cure in pancreatic cancer and remains the treatment of choice for suspected pancreatic malignancies. In patients with a suspected, clinically operable pancreatic malignancy, the need pathologic confirmation before proceeding with surgery remains debatable.

Confirming pathologic diagnosis was considered more important in the past because of the high Complications associated with surgery. Over the past decade, the need for histologic confirmation before resection has become less important as PD has become a much safer procedure and as more sophisticated imaging has allowed for a greater degree of diagnostic accuracy.

Furthermore, issues relating to biopsy-related complications, potential inaccuracy and a false negative result, potential delay in treatment, and risk of cancer spread, as well as the added cost, must also be taken into account when considering the role of preoperative biopsy.

To, overcome this problem, many pancreatic experts around the world gathered and collected their data, results of these data are shown below.

Results:

Of the all pancreatic surgeries done for suspected but not confirmed cancers only 5-13% was diagnosed as non cancerous and rest 87-95% was cancerous.

Preoperative biopsies in 95% of patients who detected cancer in postoperative settings were inaccurate. Complications such as hemorrhage, duodenal perforation, acute pancreatitis, infection, or tumor seeding as may occur after percutaneous biopsy.

Among noncancerous pathology as shown in figure majority was pancreatitis (77%).

Pancreatitis: In the absence of preoperative histologic confirmation of cancer, one of the

Common challenges are differentiating a malignant from an inflammatory mass. Difficulty arises because both pancreatic cancer and Chronic Pancreatitis have considerable overlap with regard to clinical presentation and imaging. In this subset of patients, it is important to differentiate CP from Auto Immune Pancreatitis after surgery for a presumed malignancy, the incidence of Auto Immune Pancreatitis (AIP) within the benign specimens is reported to be 30–43%. This is an important subset of patients to recognize preoperatively before resection, because treatment with steroids is likely to prevent an unnecessary operative resection.

Two subtypes of AIP have been described:

Type 1 AIP occurs more predominantly in older patients, is most commonly associated with increased levels of serum immunoglobulin (Ig)G4 and IgG4-positive plasma cells;

Type 1 AIP is also easier to diagnose histologically.

Type 2 AIP is more prevalent in younger patients, more difficult to diagnose histologically, and less often associated with an increase of serum levels of IgG4.

Endoscopy Ultra sonography guided biopsy, serum levels of IgG4, and HISORt  (Histology, Imaging, Other organ involvement, and Response to therapy) are used for diagnosis,  but confirming AIP preoperatively can remain a challenge.When in doubt, a short-term trial with steroids might be the best option to differentiate AIP from a cancer.

In contrast, the presence of Chronic Pancreatitis (CP) is more readily diagnosed preoperatively, but the difficulty involves differentiating if and when a patient with CP develops a malignancy. The International Pancreatitis Study Group cites a risk of developing cancer in CP at 4% over a 20-year period.

Preoperative differentiation between a mass effect from CP and an actual cancer is often difficult even with the use of state-of-the-art imaging and biopsy. In contrast with patients with AIP, PD would be considered an appropriate treatment for the majority of symptomatic patients with

CP and the presence of a head mass, even in the absence of malignancy.

Neuroendocrine cancer.: The diagnosis of pancreatic neuroendocrine tumors (PNET) is facilitated by the presence of symptoms and identification of the hormonal abnormalities when present; however, 15–40% ofPNETs are nonfunctioning (NFPNET).  Although there is general consensus that the hormonally active PNETs should be treated by resection, controversy exists regarding the indications for resection of smallNF-PNETs.  Because imaging studies are performed more frequently, the Incidental finding of smaller NF- PNET has become more common. Historically, however, NF-PNETs

have usually been large and present at an advanced stage when first diagnosed.  Survival after resection is affected primarily by the presence of metastases with a median survival of 23 months, compared with 124 and 70 months for those patients with localized or regional disease, respectively.

 Currently, PNETs are being found more frequently with advanced cross-sectional imaging. In these patients, pathologic confirmation is usually required to confirm that the lesion is a PNET. EUS-FNA is indicated in this subset of patients with suspected PNETand can provide cytologic confirmation.

 In general, most pancreatic surgeons agree that operative resection is the treatment of choice for NF-PNETs > 2 cm or that present rapid growth(> 0.5 cm per year). NF-PNETs that are < 2 cm are likely to be benign or intermediate-risk lesions; it is reported that only 6% of them are malignant when incidentally discovered.  In this subgroup of patients, an initial course of nonoperative management with close follow-up may be a consideration.

Following consensus guidelines are recommended for surgical treatment in non-confirmed pancreatic cancer.

Ø  In the presence of a solid mass in the head of the pancreas that is suspicious for malignancy, biopsy

proof is not required before proceeding with surgery when AIP is not suspected (strong recommendation).

Ø  Before the beginning of chemotherapy or chemoradiation  objective confirmation of malignancy is

mandatory (strong recommendation). In these patients, ERCP brushing is preferred in the presence of jaundice, because placement of an endobiliary stent is indicated. Otherwise EUS biopsy is the diagnostic modality

of choice (strong recommendation).

Ø  In patients with CP in whom a malignancy is suspected, resection is indicated even in the absence of histologic proof of malignancy (strong recommendation).

Ø  When a diagnosis of AIP is highly suspected, measurement of serum levels of IgG4 plus a biopsy is recommended (strong recommendation). EUS-guided Trucut biopsy is preferred. If biopsy results are not diagnostic or suspicious for malignancy, a short course of steroid treatment (4–6 weeks) is recommended (qualified recommendation).

Acute on chronic liver failure what is it?? is liver transplantation needed for it ??

Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection

culminating in the end-organ dysfunction. Occasionally, no specific precipitating event can be found. Although the exact pathophysiology of the development of ACLF remains to be elucidated, unregulated inflammation is thought to be a major contributing factor. A characteristic feature of ACLF is its rapid progression, the requirement for multiple organ supports and a high incidence of short and medium term mortality of 50–90%.

The condition remains undefined but two consensus working definitions for this syndrome exist. The first was put forward by the Asia–Pacific association for the study of liver disease :Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease’; and a second at a EASL-AASLD single topic symposium : ‘Acute deterioration of pre-existing, chronic liver disease, usually related to a precipitating event and associated with increased mortality at 3 months due to multi-system organ failure’. These definitions are too imprecise to allow homogeneous diagnostic criteria and clinical studies are currently underway to reach an evidence-based definition. The latter definition implies that organ failure is a central component of this syndrome and leads to the hypothesis that the organs may behave

differently to chronic decompensated liver disease..

The prognostic factors determining the outcome of patients with cirrhosis and multiorgan failure are currently under evaluation, but it seems that the scoring systems addressing the severity of liver disease, such as Child-Pugh score [6] or Model of End Stage Liver Disease (MELD) perform less well than the scoring systems addressing organ dysfunction such as the Sequential Organ Failure Assessment (SOFA) or the Acute Physiology, Age and Chronic Health Evaluation (APACHE)

There is some role of liver supporting system like MARS but not proven completly

Liver transplantation in patients with ACLF has not been systematically analyzed but a recent retrospective study was performed in 332 patients of whom 157 patients had ACLF and 175 patients had no ACLF pre-transplant . Thirty-four patients received a liver-kidney transplant, of whom 10 (29.4%) had ACLF. The definition was based on a rapid increase in MELD by >5 points. The results showed that the group with ACLF had a  26% mortality compared with a mortality of 17% in the non-ACLF group. The difference was statistically different in univariate analysis, but when only single organ transplants were analyzed, the results were not statistically different. On multivariate analysis, ACLF was not an independent predictor of post-transplant mortality, arguing strongly that this is a good indication for transplantation . The timing of transplantation is crucial as patients with ACLF may provide a window of opportunity. Therefore, living-donor transplantation is an attractive option, the experience of which has been reported extensively from South-East Asia, mainly in patients with ACLF resulting from re-activation of hepatitis B virus infection. The data from Hong Kong suggests that although the patients with ACLF and HRS had stormier post-operative course, living donor transplantation could be performed safely and overall there were no significant differences in survival with 5-year survivals of about 80% . Similar observations have been made regarding the safety and feasibility of living donor transplantation from the Chinese groups . Currently, in most countries there is no priority for ACLF patients who have significantly higher short-term mortality. A better understanding of the natural history and prognostic criteria will allow ACLF to be incorporated as a possible new indication for high urgency allocation.

Following figures shows mechanism of acute on chronic liver failure.

Sugical Anatomy of Liver Simplified for General Surgeons

I feel that the only reason general surgeons fear from liver is because lack of understanding or poor understanding of its anatomy.

And complicated segmental anatomy given in general surgery text books without proper explanation.(though very important and every surgeon should read it before reading my post.)

First forget about segments. You will be doing segmentectomies very rarely.

Just remember following terminologies:

1.     Right lobe

a.     Right anterior sector

b.     Right posterior sector

2.     Left lobe.

a.     Left Letral segment

b.     Segment 4

3.  Caudate lobe

Vascular structures that you can dissect extrahepatically in porta. (Dissect slowly and carefully you just need to denude porta and you can do each type of liver surgery)

Ø  Hepatic artery proper (hepatic artery after gastroduodenal artery before that it is called common hepatic artery)

o   Right hepatic artery (mostly branch from hepatic artery proper or lie posterior to the bile duct when arises from SMA)

§  Right anterior sector artery

§  Right posterior sector artery

o   Left hepatic artery

§  Segment 4 artery (some time it arises from right)

Ø  Bile Duct:

o   CBD

o   Right hepatic duct

o   Left hepatic duct

                                

Technically You can see these structures in the porta outside liver but my plan in liver resections generally is quite simple dissect all the vascular structures and rest is bile ducts. Cut it in the end after parenchymal transection.

Ø  Hepatic veins: (at the top when you dissect falciform ligament)

·      Right hepatic vein

·      Middle left vein together

Inititally dissect falciform ligament until you can see right and left-middle vein insert in to IVC and dissect groove between right and middle- left.

·      Inferior hepatic veins: draining directly from right lobe to IVC on right side and caudate vein found on left side.

Now Few Simplified Anatomical Definitions of Liver lobes according to venous drainage

Right lobe: Liver tissue right to middle hepatic veini

Left lobe : Liver tissue left to middle hepatic vein.

Most people say middle hepatic vein is a part of left lobe but for me as a surgeon for better understanding I take middle hepatic vein as no man’s land. Like Indo China border dispute and I act as U.N. so I give land according to the need.

If middle hepatic vein is involved with tumor or tumor is very close my right hepatectomy will include middle hepatic vein also or in case of transplantation when graft volume is border line or CT shows right anterior sector is draining mostly in to middle vein.I will take middle hepatic with the right lobe.

If tumor is far away from middle hepatic I will keep middle hepatic vein with the left side. Or in case of transplantation when right vein is dominantly draining anterior or graft volume is adequate I will keep middle vein with the left lobe.

Same goes with left hepatectomy in transplantation when you are taking left lobe middle hepatic vein almost always remains with the left lobe.

Right anterior sector: area between middle hepatic and right hepatic vein.

Right posterior sector: area Right to right hepatic vein including right hepatic vein area.

Left lateral sector liver tissue left to falciform ligament

Segment 4 area between facifom ligament and middle hepatic vein.

Caudate lobe is a seprate entity.

With these facts in the next part I will try to right simplified techniques of different hepatectomies.

A revolution in the treatment of Hepatitis C.FDA approves single tablet treatment (fixed dose combination of Sofosbuvir and ledispavir) In Genotype 1

Hepatitis C – days of interferon based treatment are gone.

Hepatitis C will be treated by single oral tablet.

Sofosbuvir alone or in combination with ladispavir – A revolution in the treatment of Hepatitis C

New England journal of medicine published 3-research article in april – may 2014.

Shows result of fixed dose combinations of two drugs (fixed dose combination means they will be available as single tablets)

 (See my previous blog in Hepatitis C for current recommendation with sofosbuvir)

In this post I will be posting about fix dose combination of Sofosbuvir with Ledispavir which got FDA approval recently.

1.     Previously Treated but failed with interferon.

·      In patients without cirrhosis this new drug combination gave Sustained Virological response (see my previous blog) in 95% of patient with 12 week therapy and 99% in 24 week therapy

·      With cirrhosis It gave response rates of 86% at 12 week and 99% at 24 week.

·      If we add ribavirin (another drug see my previous posts), It gave response rates of almost 100% without cirrhosis at 12 and 24 week without cirrhosis

·      With cirrhosis if we add ribavirin than response rates were 82% at 12 weeks and 99% at 24 weeks.

2.     Long term Hepatitis without Cirrhosis.

·      94% sustained virological response at 8 weeks and 95% at 12 weeks without ribavirin

·      93% with ribavirin at 8 weeks and 97.5 % at 12 weeks.

3.     Untreated Hepatitis C

·      95% Sustained virological response at 12 week and 98% at 24 week in sofosbuvir-ladispavir  fixed dose combination (single tablet).

·      97% at 12 week with ribavirin and 99% at 24 week.

Ø  TAKE HOME POINTS:

·      NEED OF INTERFERON WILL BE LESS AND LESS AFTER THIS DRUG AND SO WE WILL BE ABLE TO AVOID ITS TOXICITY

·      EXCELLENT RESULT IN PATIENT OF CIRRHOSIS. THIS GROUP IS LIKELY TO BENEFIT THE MOST.

·      SINGLE TABLET SO TREATMENT WILL BE EASY FOR PATIENT

·      MAY BE HELPFUL IN POST TRANSPLANT PATIENTS TO AVOID RECURRENCE. (TRIALS ARE GOING ON)

·      COST NEED TO BE DECREASED.