Principles of Surgical - PowerPoint Presentation

Slide1

Principles of Surgical Oncology

Professor Maitham AL

Khateeb

FACS

,

CABS

,

DGS

Consultant

surgeon

2018

Slide2

contents

Definitions

Characteristics of cancers

Malignant transformation

The growth of cancers

Clinical implications

Causes of cancers

Management of cancers

Carcinogenesis

Screening of cancer

Diagnosis of cancers

Staging of cancers

Principles of cancer surgery

Removal of primary disease

Removal of metastatic disease

Palliative surgery

Principles of non surgical treatment CHEMOTHERAPY & RADIOTHERAPY

End of life care / the good death

Slide3

Oncology

:

(Gr.

onkos

-tumor

; logos

-study) Is the study of these diseases.

Tumour

:

is a new growth of tissue or a mass

which might be

inflammatory,

benign

or

neoplastic

Carcinomas

:

are malignant tumors that

arise from epithelium

.

Sarcomas

:

are malignant tumors that

arise from connective tissue

.

Neoplastic cells

behave independently

,

they do not have fixed relationships to other cells and do not form organs

. They are

either benign

or

malignant

.

Benign

means:

A noninvasive growth and without metastasis

.

malignant

means:

An

invasive growth with metastasis.

Slide4

Doubling time of the tumor growth

:

(the time that the tumor takes to double in volume). This is

to express the rate of tumor growth

.

Pathologist`s cancer

:

Cancers noticed at autopsy

, and not clinically evident for example (

4%

of cadavers will have

microscopic papillary thyroid cancer

&

15%

of male cadavers above 60 years will have

microscopic prostatic cancer

.

Multicentricity

:

Is a feature of cancer originating at many anatomical locations

.

Synchronous cancer

:

Is another cancer

that develops

at the time of the initial presentation.

Metachronous cancer

:

Is another cancer that develops later in life.

Hypertrophy

:

increase in size of organ without increase in cell number

.

Hyperplasia

:

increase in size due to increase in cell number

.

Metaplasia:

change in the characteristics of epithelium from which the tumor grow

. Example: from Transitional to squamous (

bladder cancer

),from columnar to squamous (

bronchus cancer

).

Dysplasia:

(

mild

,

moderate

&

severe

):

Early changes of neoplastic transformation

e.g. size & shape of cells & nuclei

. These may revert to normal

.

Carcinoma in situ:

neoplastic changes in cells & nuclei without invasion of extracellular matrix.

Precancerous conditions

:

Leukoplakia may progress to carcinoma

Slide5

5

Ductal cancer cells

Normal ductal cell

Ductal cancer cells breaking through the wall

Slide6

WHAT IS CANCER ?

History

The name

‘cancer

’ comes from the Greek and Latin words for

a crab

, and refers to

the claw-like blood vessels

extending over the surface of an advanced breast cancer

.

The molecular biology

of cancer enabling us to investigate, and, in some cases, understand, the biochemical mechanisms whereby cancer cells are formed and mediate their abnormal behaviour

Cancers are now firmly based on the cellular origin of the CancerCancer cells are psychopaths:They have no respect for the rights of other cells.

They violate the democratic principles of normal cellular organizationTheir

proliferation is

uncontrolled

Their

ability to spread is

unbounded

Their continuous,

relentless

Progress

destroys first the tissue and then the

person

In order to behave in such an unprincipled fashion, cells have to acquire a number of characteristics before they are fully malignant

.

No one characteristic is sufficient, and not all characteristics are necessary

Slide7

Malignant transformation:

_

Establish an autonomous lineage

:

-

resist

signals that inhibit growth

-

acquire independence from signals stimulating growth _ Obtain immortality 

_ Evade apoptosis _ Acquire angiogenic competence _ Acquire the ability to invade _ Acquire the ability to disseminate and implant _ Evade detection/elimination _

Genomic instability _ Jettison excess baggage_ Subvert communication to and from the environment/milieu

 

_

Develop ability to change energy metabolism

Slide8

Establish an autonomous lineage

:

This involves

developing independence

from the normal signals that control supply and demand.

Cancer cells

escape

from this normal system of checks and balances

:

they grow and proliferate in the absence of external stimuli

regardless of signals telling them not to do so

Oncogenes, an aberrant form of the normal cellular genes, are a key factor in this process

We all carry within us genetic sequences that, through mutation, can turn into active oncogenes and thereby cause malignant transformationObtain immortality:Normal cells are permitted to undergo

only a finite number of divisions. For humans, this number is between 40 and 60.The limitation is imposed by the progressive shortening of the end of the chromosome

(

the telomere

) that occurs each time a cell divides

Slide9

Cancer cells can use the enzyme telomerase

to rebuild the telomere at each cell division

,

so there is no telomere shortening and the lineage will never die out

.

(The

cancer cell has achieved

immortality)

Evade

apoptosis

:Apoptosis is a form of programmed cell death which occurs as the direct result of internal cellular events instructing the cell to die The cell dismantles itself neatly for disposalNormal Cells that find themselves in the wrong place normally die by apoptosis and this is an important self-regulatory mechanism in growth and developmentCancer cells will be able to evade apoptosis, which means that the wrong cells can

be in the wrong places at the wrong times.

Slide10

Acquire angiogenic competence

:

The ability of a tumour to form

blood vessels

is termed

‘

angiogenic competence

’ and is a key feature of malignant

transformation

Acquire the ability to

invade

:Cancer cells have no respect for the structure of normal tissues. They acquire the ability to breach the basement membrane and thus gain

direct access to blood and lymph vessels using three main mechanisms to facilitate invasion: -they cause a rise in the interstitial pressure within a tissue -they secrete enzymes that dissolve extracellular matrix -they acquire

motilityUnrestrained proliferation and a lack of contact inhibition enable cancer cells to exert pressure directly on the surrounding tissue and push themselves beyond normal

limits

They secrete

collagenases

and

proteases

that chemically dissolve any extracellular boundaries that would otherwise limit their spread through

tissues

signals from the environment to the cytoplasm and nucleus of the cancer cells

(‘

outside-in signaling

’

),

these signals can induce increased motility

 

Slide11

Acquire the ability to disseminate and implant

:

Once cancer cells gain access to vascular and lymphovascular spaces, they have

acquired the potential to use the body’s natural transport mechanisms to distribute themselves throughout the body,

They also need

to

acquire the ability to

implant

Evade

detection/elimination

:

Cancer cells are simultaneously

both ‘self’ and ‘not self’. Although derived from normal cells (‘self’), they are, in terms of their genetic make up , behaviour and characteristics, foreign (‘not self’)This may be by suppressing the expression of tumour-associated antigensGenomic

instability:A cancer is a genetic fermentCells are dividing without proper checks and balances.

Mutations are arising all the time

This gives rise to the phenomenon of genomic instability

 

Slide12

Jettison excess baggage

:

Cancer cells

are programmed

to excessive and remorseless proliferation

.

Subvert communication to and from the

environment/milieu

:

Providing false information

is

a classic military strategy.

Degrading the command and control systems of the enemy is an essential component of modern warfare. Cancer cells almost certainly use similar tactics in their battle for control over their hostDevelop ability to change energy metabolism:Cancer cells may have to spend prolonged periods starved of oxygen

– in a state of relative hypoxiaCompared to the corresponding normal cells, some cancer cells may be better able to survive in hypoxic conditions.

Cancer cells can alter their metabolism even when oxygen is abundant

 

 

Slide13

Malignant transformation

:

Only very rarely is a single mutation sufficient to cause cancer

;

multiple mutations

are usually

required

these

mutations

must be acquired in a specific sequence

.

Cancer is usually regarded as a clonal disease.Some cancers may arise from more than one clone of cells

Two mechanisms may help to sustain and accelerate the Process of malignant transformation:1-Genomic instability:may themselves be capable of facilitating the persistence of further mutations and so the malignant transformation can be accelerated2-

Tumour-related inflammation:If a tumour provokes an inflammatory response, then the cytokines and other factors

produced as a result of that response may act to

promote and sustain malignant transformation.

Slide14

The growth of a tumour

:

A

tumour 10 mm in

diameter

it would take 30 generations to reach the threshold of clinical

detectability

This is an

over simplification

because

cell loss is a feature of many tumours

and, for squamous cancers, as many as 99 per cent of the cells produced may be lost, mainly by exfoliationIt will, in the presence of cell loss, take many cellular divisions to produce a clinically evident tumour

.Clinical implications: The majority of the growth of a tumour occurs before it is clinically detectable By the time they are detected

, tumours have passed the period of most rapid growth, that period when they might be most sensitive to anti-proliferative drugs There has been plenty of time, before diagnosis, for individual

cells to detach, invade, implant and form distant metastases

in many patients cancer may, at presentation, be a systemic disease

 

Slide15

‘Early tumours’ are genetically old: plenty of time for mutations to have occurred, mutations that might confer spontaneous drug resistance (a probability greatly increased by the existence of cell loss

)

-The

rate of regression of a tumour will depend upon its

age

,

the

rate of regression of a tumour will depend upon its growth rate at the time of

treatment

In its early stages, growth is exponential but, as the tumour grows, the growth rate slows

. This decrease in growth rate probably arises

because of difficulties with nutrition and oxygenation ,The

tumour cells are in competition: not only with the tissues of the host, but also with each otherTHE CAUSES OF CANCER:Both inheritance and environment are important determinants of cancer development

Although environmental factors have been implicated in more than 80 per cent of cases, this still leaves plenty of scope for the role of genetic inheritance:

 

Slide16

not just the 20 per cent of tumours for which there is no clear environmental contribution but also,

as environment alone can rarely cause cancer

, the genetic contribution to

the 80 per cent

of tumours to which environmental factors contribute

Knowledge about the causes of cancer can be used to design appropriate strategies for

prevention

or

earlier diagnosis

.

As more is discovered about the genes associated with cancer

, genetic testing and counseling will play an increasing role in its prevention.

THE MANAGEMENT OF CANCER:Management is more than treatmentThe traditional approach to cancer concentrates on diagnosis and active treatment.Prevention is forgotten and

rehabilitation ignored

Slide17

Carcinogenesis:

causes of cancer:

1.

Chemical carcinogens;

aniline dye

(bladder Ca.),

nickel

(lung).

2.

Physical carcinogens:

- Ionizing radiation

; leukemia,, lymphoma, thyroid & breast cancer

- Ultraviolet irradiation

; malignant melanoma- Sites of chronic irritation

; chronic osteomyelitis, chronic ulcerative colitis, fistula in ano & in old burn scar (Margolin`s ulcer)

3.

V

iruses:

e.g

.

HIV

(Kaposi’s sarcoma),

EB virus

in Burkitt`s lymphoma and

Hepatitis B virus

in hepatocellular carcinoma.

Herpes virus

in Cervix, penis, & anal cancer.

4.

Other infections;

Bilharzia

(Bladder Ca.) &

H. pylori

(Stomach Ca.)

5.

Tobacco;

(Lung cancer & Head and neck cancer)

6.

Alcohol;

(Head & neck Ca., oesophageal Ca. & hepatoma.

7.

Inhaled particles;

Asbestos

(mesothelioma)

8

.

Fungal and plant toxins;

Aflatoxins

(hepatoma

)

9. Age (old age). Obesity

Slide18

Lymphoma

Kaposi sarcoma

Slide19

Prevention:

30 per cent

of cancer deaths

were due to tobacco use

and

that up to 50 per cent

of cancer deaths were related to

diet

(

smokers often have a poor diet)Estimated that cancers related to occupation accounted for less than 4 per cent of cancer deaths, and that environmental pollution accounted for

less than 5 per cent of deaths.Screening:Screening involves the detection of disease in asymptomatic population in order to improve outcomes by early diagnosis

.It follows that a successful screening programme( 1 ) must achieve early diagnosis

,

and

( 2 )that

the disease

has a better outcome when treated at an early stage

.

Slide20

slow-growing tumours are likely to be picked up by screening,

whereas fast-growing tumours

are likely to arise

and produce symptoms in between screening rounds

.

Thus, screen-detected tumours will tend to be less aggressive than symptomatic tumours

Because of these biases, it is essential to carry

out population-based randomised controlled trials

and to compare mortality rate in a whole population offered screening

Diagnosis

and classification

:Accurate diagnosis is the key to the successful management of cancer. Precise diagnosis is crucial to the choice of correct therapyA diagnosis of cancer can confidently be made by taking tissue for pathological or cytological examination.

Different tumours are classified in different waysPrecise and accurate subtyping of tumours enables appropriate selection of treatment and, in turn, this is associated with better outcome.

 

Slide21

ClassificationTissue of origin

site of origin

benign

malignant

epithelium

skin, larynx….. papilloma squamous cell

carc

.

Breast, stomach….. adenoma adenocarcinoma mesodermal fibrous tissue fibroma fibrosarcoma

muscular tissue leimyoma, leiomyosarcoma, rhabdomyoma rhabdomyosarcoma fatty tissue lipoma liposarcoma

vascular tissue angioma angiosarcoma bone

osteoma,chodroma

osteogenic

sarcoma,

chondrosarcoma

hemopoietic

tissue Leukemia, multiple

myeloma, lymphoma

special types

melanocyte

skin, eye nevus malignant melanoma

neural tissue

brain,spinal

cord

astrocytoma

glioblastoma

multiforme

ganglioneuroma

neuroblastoma

blastoderm

ovary, testis

teratoma

teratoma

 

Slide22

INVASION & METASTASIS

Local invasion

;

Occur along lines of least resistance

. It is due to increased pressure by rapidly dividing cells, abnormal motility of malignant cells & the breakdown of extra cellular matrix.

Lymphatics

;

Permeation

or

emboli

Blood stream

; Portal vein to the liver. Systemic veins to the lung

.Implantation; e.g. transcoelomic through the peritoneal cavity. Grading of the tumor:Is based on the histological examination of the degree of differentiation of the tumor cells & mitotic index

(well, moderately

or

poorly differentiated

)

Staging of the tumor:

Is an estimation of the degree of spread of the tumor.

It is based on clinical examination & imaging technique

.

Slide23

Investigations

Investigations includes imaging, pathological or cytological

examination.

Tumor markers; CA15-3, CA27-29, CEA

Diagnosis:

Precise diagnosis

is crucial to the choice of correct therapy

.

Only rarely can a diagnosis of cancer confidently be made in the absence of tissue for

pathological or cytological examination

Slide24

scattered, well-defined, round calcifications that can be characterized as benign.

Oblique mammogram demonstrates a classic

benign, partially calcified fibroadenoma with typical coarse,

popcorn-like calcifications. These findings are not suspicious and do not require biopsy.

Oblique mammogram demon

strates

a classic benign, partially calcified

fibro adenoma

with

typical coarse, popcorn-like calcifications

. These findings are not suspicious.

Slide25

Compression view of a mammogram showing a high-density spiculated mass (red arrow) with heterogeneous linear clacifications in a ductal distribution

(white arrows). These "casting" calcifications are

characteristic of high-grade ductal carcinoma in situ [DCIS]

.

Mammogram showing

linear branching calcifications in a segmental distribution

(red arrow).

Clustered microcalcifications

such as these are

highly suggestive of carcinoma

,

the linear branching is suggestive of a ductal lesion

. Biopsy confirmed a high-grade ductal carcinoma in situ (DCIS).

Slide26

Investigation and staging:

Staging

is the process

whereby the extent of disease is mapped out

.

It is not sufficient simply to know what a cancer is

;

it is imperative to know its site and extent

If it is localised

,

then locoregional treatments is used

such as surgery

and radiation therapy may be curative.If the disease is widespread, then, although such local interventions may contribute to cure, they will be insufficient, and systemic treatment, for example with drugs or hormones

,will be required.The International Union against Cancer (IUCC) is responsible

for

the TNM (tumour, nodes, metastases ) staging system for

cancer

., This

system is compatible with, and relates to

, the American Joint Committee on Cancer (AJCC)

system for stage grouping of

cancers

 

Slide27

Gives an estimate of prognosisUseful in planning treatment

Helps in comparison of outcome in different centers

Types of staging

:

Manchester staging of breast cancer:

Stage 1. Tumor localized to the breast, <2cm

Stage 2. Tumor 2-5cm with mobile axillary lymph nodes same side

Stage 3. Tumor size > 5cm with fixed axillary lymph nodes

Stage 4. Tumor with distant metastasis

Benefit of staging

Slide28

TNM classification

M = metastasis

N = node

T = tumor

Stage

M0

N0 = no nodes

No palpable tumor

TIS

=

N0 = no nodes

T1 < 2cm

I

=

N1 = mobile axillary lymph nodes

T2 (2-5cm)

II

=

N2 = fixed lymph nodes

T3

IIIa

=

Any size invading skin + N3 (supra-

Clavicle ipsilateral lynph nodes

T4

IIIb

M = 1

Any

Any

IV

Slide29

Therapeutic decision making and the multidisciplinary teamAs the management of cancer becomes more complex, it

becomes impossible for any individual clinician to have the intellectual and technical competence that is necessary to manage all the patients presenting with a particular type of tumour

Teams should

Not only be

multidisciplinary

,

they should

be

multiprofessional

Members of the multiprofessional team

_ Site-specialist surgeon

_ Surgical oncologist

_ Plastic and reconstructive surgeon_ Clinical oncologist/radiotherapist_ Medical oncologist_ Diagnostic radiologist_ Pathologist_ Speech therapist

_ Physiotherapist

_ Prosthetic specialist

_ Clinical nurse specialist (rehabilitation, supportive care)

_ Palliative care nurse (symptom control, palliation)

_ Social worker/

counsellor

_ Medical secretary/administrator

_ Audit and information coordinator

Slide30

Principles of cancer surgery:For most solid tumours

,

surgery remains the definitive treatment and the only realistic hope of cure

However

, surgery has several roles

in cancer treatment

including:

-

Diagnosis

- Removal of primary disease

- Removal of metastatic disease

- Palliation

-Prevention - ReconstructionDiagnosis and staging :In most cases, the diagnosis of cancer has been made

before definitive surgery is carried out but, occasionally, a surgical procedure is required to make the diagnosis. This is particularly true of patients

with malignant ascites

where

laparoscopy

has an important role in obtaining tissue for diagnosis.

Slide31

FNAC (fine needle aspiration cytology)Easy, inexpensive, no preparation.

Not reliable in distinction between

in situ

&

invasive ductal carcinoma

.

FNAB

is operator dependent .

2.

True-cut biopsy or

Core needle biopsy

Multiple tissue samples Types of biopsy

Slide32

3-Incisional biopsy Only part of the tumor is removed for histopathological study- It is done when the tumor is large

-

It is rarely performed nowadays

-

It is done under local or general anaesthesia

Slide33

4-Excisional biopsy Most common biopsy procedure The entire lump is taken out using a small incision

Send the specimen for histopathological study & report

Slide34

Slide35

Laparoscopy is also widely

used for the staging of intra-abdominal malignancy

,

particularly lower esophageal and gastric cancer

Laparoscopic ultrasound

is a

particularly useful adjunct

for the diagnosis of

intrahepatic metastases

Until recently

, staging laparotomy was an important aspect of the staging of lymphomas which is now replaced by laparoscopic technique

Removal of primary disease:Radical surgery for cancer:involves removal of the primary tumour and as much of the surrounding tissue and lymph node drainage as possible

in order not only to ensure local control but also to prevent spread of the tumour through the lymphatics.that ultraradical surgery

probably has little effect

on the development of metastatic disease

It is important, however, to appreciate

that high-quality, meticulous surgery

taking care not to disrupt the primary tumour at the time of excision is of the utmost Importance in obtaining a cure in localised disease and preventing local recurrence

 

Slide36

T4 N2Mo

Slide37

Removal of metastatic disease:

In certain circumstances

, surgery for metastatic disease may be appropriate

.

This is particularly true

for liver metastases arising from colorectal cancer,

With multiple liver metastases, it may still be possible to take

a surgical approach by

using

in situ

ablation

with cryotherapy or radiofrequency energy

Palliation:In many cases, surgery is not appropriate for cure but may be extremely valuable for palliation.A good example is the patient

with a symptomatic primary tumour who also has distant metastases. In this case:

Removal of the primary may improve the patient’s quality of life

,

but will have little effect on the ultimate outcome

.

Other examples include

bypass procedures

, such

as an ileotransverse anastomosis

to alleviate symptoms of obstruction

caused by

an inoperable caecal cancer

Or

bypassing an

unrespectable

carcinoma at the head of the pancreas

by

cholecysto- or choledochojejunostomy to alleviate jaundice.

Slide38

Non surgical treatment of cancersIn patients with documented distant metastatic disease

,

chemotherapy

is usually the primary modality of therapy

.

Chemotherapy is rarely sufficient to cure cancer

. Chemotherapy is often a palliative intervention

Include

; 65% are Cytotoxic drugs

,

15% are hormonal therapies

and 15% are designed to interact with specific molecular targets – so called targeted therapies.

Types of chemotherapeutic and biological agents :1. Drugs that interfere with mitosis (Vincristine, vinblastine) in lymphoma2. Drugs that interfere with DNA synthesis (anti-metabolites

) e.g. Fluorouracil (5-FU) in breast cancer & Gastrointestinal cancer

3.

Drugs that

damage DNA

(

Mitomycin C

) in bladder & Head and neck cancer

4.

Hormones

; (

Tamoxifen

) Blocks oestrogen receptors in Breast cancer & Head and neck cancer.

Anastrazole

(An

aromatase inhibitor)

blocks post-menopausal (non-ovarian) oestrogen production in breast cancer

.

5.

Antibodies directed to cell surface antigens

(

Trastuzumab

) Antibody directed against HER2 receptor in breast cancer

6.

Immunological mediators

(

Interferon alpha-2b

)

in melanoma & renal carcinoma

Adjuvant therapy

can be administered after surgery

(

postoperative chemotherapy)

Neoadjuvant chemotherapy

before surgery

(

preoperative chemotherapy

)

Slide39

Principles underlying the non-surgical treatment of cancer :

the treatment

should be selectively toxic to the

tumour

and, as far as possible

, should spare

the normal

tissues from

damage

It is this simple principle that decides

both the selection of agents used to treat cancer and the schedules employed to deliver them.Chemotherapy is systemic treatment surgery is mainly a local treatmentRadiotherapy

is usually local or locoregional, but can, as in radioiodine therapy for thyroid cancer, be systemic.Radiotherapy:Radiation can,

both directly and indirectly, influence gene expression

, These changes in gene expression are responsible for a considerable proportion of

the biological effects

of radiation upon tumours and normal tissues,

In this sense:

radiotherapy is a precisely targeted form of gene therapy for cancer

.

 

Slide40

Fractionated radiotherapy selectively spares late, as opposed to immediate effects of radiotherapy.

For any given total dose

,

the smaller the dose per treatment (the larger the number

of fractions), the less severe the late effects will be.

the greater the number of fractions of daily treatment, the longer the overall treatment time and

the greater the opportunity for the tumour to proliferate during treatment

Chemotherapy and biological therapies

:

Selective toxicity

is the fundamental principle underlying the use of chemotherapy in clinical practice

chemotherapy is rarely sufficient to cure cancerChemotherapy is often a palliative rather than a curative interventionThere are now over 95 different drugs licensed by the US Food and Drug Administration

(FDA) for the treatment of cancer.

Slide41

Over 50 per cent of these agents have been

licensed since 1990

:

The kinase inhibitor

will only be effective

in patients with

melanoma

cetuximab

is only effective

in patients with colorectal cancerimatinib is particularly effective in patients with

gastrointestinal stromal tumours (GIST)The next decade will see a major shift in the medical management of cancer – from cell destruction to cellular reprogramming, but the longer-term consequences of such sophisticated manipulations may be uncertain and unpredictable.

Principles of combined treatment:

Cytotoxic drugs are rarely used as single agents

radiotherapy and chemotherapy are often given together

The choice of drugs for combination therapy is based upon three main principles

:

use

drugs active against the disease

(2)

use drugs with distinct modes of action

(3)

use drugs with non-overlapping toxicities

it may be possible to obtain a truly synergistic effect

 

Slide42

It is inadvisable to combine drugs

with similar adverse effects;

combining two highly

myelosuppressive drugs

may

produce

an unacceptably high risk of neutropenic sepsis

In considering

the combination of radiotherapy and chemotherapy

,

radiation could be considered as just another drug.

Palliative therapy:The distinction between palliative and curative treatment is not always clear cut, Five-year survival is not necessarily equal to curethe distinction between curative and palliative therapy seems somewhat arbitrary

Palliative treatment has as its goal the relief of symptoms Palliative medicine in the twenty-first century is about far more than optimal control of pain: its scope is wide, Its impact immense

Slide43

End-of-life care :End-of-life care is distinct from palliative care

.

Patients treated palliatively

may survive for many years

end-of-life care concerns the last few months of a patient’s life

The concept of

the ‘good death’

has been embedded in many cultures over many centuries

But it is

not

an accepted practice and not legally permitted practice in our community and country( the good death ).